Lifelines for Health: Progress in the Diagnosis and Management of vonWillebrand Disease by CHES

A CHES Publication

Spring/Summer 2021 I Volume 17

PROGRESS

in the

Diagnosis

Management

vonWillebrand Disease

Complimentary & Alternative Medicine ...Uses for Pain in Bleeding Disorders, pt.3 l Emerging Advocates Could Sway Copayment Accumulator Battle l Validation: Why You Need It. How to Get It. How to Give It. l PK What? l And more!

Letter From the Editors Welcome! As we go to print this summer, it is probably fair to say that our lives post COVID, may never be the same. Perhaps that is a good thing in some ways. Time spent with family, with less distractions, and schedules brought some parents and children closer. Some businesses have begun to rethink flexible scheduling that allows employees to work from home. Virtual programming has allowed us to stay connected. It will be years before we understand its full impact. We have faced many challenges; but those affected by rare, chronic conditions are familiar with challenges and somehow emerge stronger and wiser for them. Programming in 2021 may continue to look a little different. Decisions on live programming are still tentative. Vaccinations may be required. We may utilize a hybrid model of programming, with small numbers of participants meeting live and streaming educational sessions. We will follow CDC guidelines and are hoping for the best! nSpiration Foundation, as a 501 c 3 non-profit, will collaborate with CHES to present After the Shock: an Inhibitor Family Camp, One Drop: THE Rare Bleeding Disorders Consortia, (which combines the previous F7 Retreat and GT Symposia programs) LadyBugs, and Momentum. Resources are limited to fund air travel, which is what makes nSpiration Foundation an important partner. It has the ability as a non-profit to accept donations and submit grants to a wider variety of resources. Paul Wheatley has taken over the reins as the Director of Development and Communications and we are excited to work with him!

facebook.com/ CHES.Programs

In the meantime, we hope you enjoy this issue of LifeLines for Health. We are excited to share new guidelines for the diagnosis and treatment of vonWillebrand Disease. At our LadyBugs program, we hear the frustration of our participants with type 1 and 2 vWD and are thrilled to see more research for better quality of life. Angela Lambing shares her last installment on pain management. PSI provides an update on Accumulator Adjusters. Our friend, Dr. Gary McClain takes a look at the concept of validation; a struggle for many of us-especially in a pandemic. Refresh your memory on why mindfulness is more important than ever.

instagram.com/ CHES_Programs

LifeLines for HealthSM Disclaimers The views and opinions of our writers are not a reflection of Comprehensive Health Education ServicesTM, Inc. (CHES) or its sponsors.

Be sure to check out our website at www.ches.education, like us on Facebook, and follow us on Instagram to stay apprised of how to keep up to date and connected to programs. If you have an idea, comment or suggestion, don’t hesitate to let us know at info@ches.education. We love to hear from you!

This newsletter is designed to provide a forum for community members to express their views from an open and honest platform. It is meant to provide a sharing of knowledge and experience to help one another. Nothing in this newsletter is meant to replace the advice of your HTC, medical professional team or insurance provider. You are always urged to seek the opinion of a healthcare professional for treatment and your specific insurance provider for information.

In the meantime, follow the science, move, reach out for help, embrace your family, and enjoy the fresh air and sunshine. Be safe, be well and we look forward to seeing you as soon as we can. - Janet Brewer & Eric Lowe

We take your privacy very seriously. We would never disclose your personal health information without your express written consent. We would never sell nor make available our secure database to anyone.

jbrewer@ches.education

“I cannot say whether things will get better if we change; what I can say is they must change if they are to get better.” -Georg C. Lichtenberg

Articles and pictures may not be reproduced, published, and/or placed on websites without the express written permission of CHES. In every publication of LifeLines for HealthSM, we will provide links to other websites that are not owned or controlled by CHES or its sponsors. We cannot be responsible for privacy practices of other website owners, nor can we be responsible for the accuracy of the information provided.

elowe@ches.education

German physicist

LIFELINES for HEALTH

Spring/Summer 2021

Integrity, Accuracy, Empathy...

FEATURE 6 I Progress in the Diagnosis & Management of vonWillebrand Disease Individuals and families affected by vWD are beginning to see the medical care changes they have been patiently (no pun intended) awaiting. And we can't think of anyone better to highlight those changes than Dr. Jonathan C. Roberts who is an investigator and co-developer of an ELISA based diagnostic test for vWD that yields better accuracy.

CONTENTS COMMUNITY CHATTER

FAMILY MATTERS

8 I Remembering Sarah Chan

30 I Validation: Why You Need It. How to Ask for It. How to Give It.

Sarah entered our lives just a few short years ago as CHES began serving families living with Glanzmann's thrombasthenia. In that brief time, she touched many lives, including her friend Barb Forss, who shares some of her heartfelt memories with Sarah.

WHAT’S NEW 5 I nSpiration vs. CHES: What's the Difference? For CHES familiars, the nSpiration name may have provoked a head tilt or an eye brow raise as it's showing up on some CHES messaging. As separate organizations, each of them compliment the other to reach big accomplishments. This is how it all works!

22 I Emerging Advocates Could Sway Copayment Accumulator Battle The copayment accumulator has become a dreaded word for most seeking medical treatment by making out-of-pocket costs higher. But one of the biggest health insurance providers has paused its copayment accumulator program after feeling the pressures from patient advocates. Although experts warn this is no time to celebrate - traction could be lost if we aren't persistent.

26 I Complimentary & Alternative Medicine (CAM) ...Uses in Pain for Bleeding Disorders - Part 3 of 3 In the last two issues, pain specialist, Angela Lambing explained the different domains of CAM, such as (1) mind-body therapies and (2) manipulative and body-based practices. Natural products like oils and vitamins are presented to conclude this series. Note: This series was erroneously represented as a 4-part series rather than having just 3 parts. We apologize for any disappointment or inconvenience this may have created.

The people in your life love and care for you. But does it ever feel like something is missing? It could be validation, or recognition that you are worthwhile. Dr. Gary McClain better defines validation with real-life examples and explains how to give, as well as receive it.

BLOODLINES 38 I Musculoskeletal Ultrasound (MSKUS) Testing Comes to LadyBugs The Miami HTC provided free ultrasound imaging on joints of women with bleeding disorders - a fairly new (but trending) technique to monitor any active bleeding and/or joint damage. Imaging on women also provides opportunities to better understand how their joints may be affected.

42 I PK What? PK. As in, pharmacokinetics... the movement of a drug in the body from start to finish. Everyone reacts to medication differently. PK's can help doctors determine what medications and/or dosing regimens work best on a given patient. This is why it's so important to understand how PK's work and what your (or your loved one's) PK levels are.

MIND BODY CONNECTION 46 I Exploring the Science of Mindfulness One full year into the COVID pandemic, and we are experiencing more anxiety, more mental health challenges than ever before. Gaining control over our swirling emotions is as easy as taking a breath. Give it a try!

CONTENTS

2021

Education Programs Virtual programming We'd like to thank all who attended our spring webinar series concentrating on the needs of the bleeding disorder community. To receive info on additional upcoming programs and webinars visit: https://ches.education or https://nspiration.foundation

Comprehensive Health Education Services has been serving the needs of

Tentative dates for LIVE 2021 programs are as follows: August 27-30, 2021 Camp Zeke - Lakewood, PA

October 1-3, 2021 Location: TBD

November 12-14, 2021 Location: TBD

and

those with rare bleeding conditions since 2009. As long time members of the bleeding disorder community, our mission is to inspire awareness and self-reliance for patients with chronic health conditions, their families, and their communities. More details on our programs can be found on our website: www.ches.education

Challenges have a way of bringing new opportunities

and we are excited to announce that CHES partnered with the Cold Agglutinin Disease Foundation (CADF) for their virtual conference that began January 19, 2021.

Cold A-what you ask? Cold Agglutinin is a rare blood disorder that causes hemolysis. Hemolysis is when healthy red blood cells are mistakenly destroyed by the body causing symptoms such as anemia, shortness of breath and bluish discoloration of the hands and feet. Cold temperatures can trigger symptoms, including air conditioning. Think you may know someone with CAD or want to know more about it? Check out the CADF website at https://coldagglutinindisease.org/. We are thrilled to partner with this amazing group of individuals to assist in their mission to provide education and support for those managing CAD.

MY DECIDING FACTOR: Making time for what matters most. As an adult living with von Willebrand disease (VWD), you may share a bleeding disorder with others, but you have your own life, and your own needs. You may also have your own Deciding Factor—something that drives you to talk to your healthcare provider about finding a treatment that’s right for you. For Erica, it was that her frequent bleeding episodes were taking time away from things that mattered most to her. She talked with her healthcare provider, and together they decided that VONVENDI ® [von Willebrand (Recombinant)] was right for Erica’s VWD.

VONVENDI • Is used in adults (age 18 and older) diagnosed with VWD to treat and control bleeding episodes and prevent excessive bleeding during and after surgery Erica Surprise, AZ Diagnosed with VWD in 1981

Are you ready to ask about VONVENDI for your VWD? Visit VONVENDI.com to learn more.

• Is the first and only recombinant von Willebrand factor (VWF), meaning it is manufactured without human plasma or blood

• May be used with or without a recombinant factor VIII (rFVIII), as instructed by your healthcare provider VONVENDI Important Risk Information Who should not use VONVENDI? You should not use VONVENDI if you: • Are allergic to any ingredients in VONVENDI. • Are allergic to mice or hamsters. Tell your healthcare provider if you are pregnant or breastfeeding because VONVENDI may not be right for you. Please see additional Important Risk Information below.

Important Risk Information (continued) How should I use VONVENDI? Your first dose of VONVENDI for each bleeding episode may be administered with a recombinant factor VIII as instructed by your healthcare provider. Your healthcare provider will instruct you whether additional doses of VONVENDI with or without recombinant factor VIII are needed. What should I tell my healthcare provider before I use VONVENDI? You should tell your healthcare provider if you: • Have or have had any medical problems. • Take any medicines, including prescription and non-prescription medicines, such as over-the-counter medicines, supplements or herbal remedies. • Have any allergies, including allergies to mice or hamsters. • Are breastfeeding. It is not known if VONVENDI passes into your milk and if it can harm your baby. • Are pregnant or planning to become pregnant. It is not known if VONVENDI can harm your unborn baby. • Have been told that you have inhibitors to von Willebrand factor (because VONVENDI may not work for you). • Have been told that you have inhibitors to blood coagulation factor VIII. What else should I know about VONVENDI and von Willebrand disease? Your body can form inhibitors to von Willebrand factor or factor VIII. An inhibitor is part of the body’s normal defense system. If you form inhibitors, it may stop VONVENDI or factor VIII from working properly. Consult with your healthcare provider to make sure you are carefully monitored with blood tests for the development of inhibitors to von Willebrand factor or factor VIII. What are the possible side effects of VONVENDI? You can have an allergic reaction to VONVENDI. Call your healthcare provider right away and stop treatment if you get a rash or hives, itching, tightness of the throat, chest pain or tightness, difficulty breathing, lightheadedness, dizziness, nausea or fainting. Side effects that have been reported with VONVENDI include: nausea, vomiting, tingling or burning at infusion site, chest discomfort, dizziness, hot flashes, itching, high blood pressure, muscle twitching, unusual taste, blood clots and increased heart rate. Tell your healthcare provider about any side effects that bother you or do not go away. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Please see VONVENDI Consumer Brief Summary on the following page and talk to your healthcare provider.

take the place of talking with your healthcare provider.

What is VONVENDI?

® Important facts about VONVENDI : VONVENDI is a recombinant medicine used to replace low levels

What are the possible side eﬀects of VONVENDI?

Side effects that have been reported with VONVENDI This summarizes important information about VONVENDI. Please or notleaflet properly working von Willebrand factor in people with von include: nausea, vomiting, tingling or burning at infusion site, Willebrand disease. Von Willebrand is an This inherited read it carefully before using thisdisease medicine. information does chest not discomfort, dizziness, hot flashes, itching, high blood bleeding disorder in which blood does not clot normally. pressure, muscle twitching, unusual taste, blood clots and take the place of talking with your healthcare provider. increased heart rate. These are not all the possible side effects VONVENDI is used in adults (age 18 years and older) with VONVENDI. You can ask your healthcare provider for diagnosed with von Willebrand disease to: information that is written for healthcare professionals. • Treatisand control bleeding episodes What VONVENDI? What are the possible side effects ofeffects VONVENDI? Tell your healthcare provider about any side that bother • Prevent excessive bleeding during and surgerylow levels VONVENDI is a recombinant medicine usedafter to replace Side effects that have been reported with VONVENDI you or do not go away. or not properly working von Willebrand factor in people with von include: nausea, vomiting, tingling or burning at infusion site, Who should notVon useWillebrand VONVENDI? Willebrand disease. disease is an inherited chest dizziness, hotabout flashes,VONVENDI itching, high and blood Whatdiscomfort, else should I know bleeding disorder in which blood ifdoes pressure, muscle twitching, unusual taste, blood clots and You should not use VONVENDI you:not clot normally. von Willebrand increased heart rate.Disease? These are not all the possible side effects is used adults (age in 18VONVENDI. years and older) •VONVENDI Are allergic to anyiningredients Consult with yourYou healthcare to make provider sure you for are with VONVENDI. can askprovider your healthcare diagnosed with von Willebrand disease to: • Are allergic to mice or hamsters. carefully monitored with blood tests to measure levels of von information that is written for healthcare professionals. • Treat control bleeding Willebrand factor andprovider factor VIII so they for you. Tell yourand healthcare provider ifepisodes you are pregnant or Tell your healthcare about any are sideright effects that bother •breastfeeding Prevent excessive bleeding during andnot after because VONVENDI may besurgery right for you. You or may at a hemophilia treatment center you doinfuse not goVONVENDI away. (HTC), at your healthcare provider’s office or in your home. Who You should trainedIon how to do infusions by yourand Whatshould should not I telluse myVONVENDI? healthcare provider before What elsebe should know about VONVENDI healthcare provider or HTC. Many people with von Willebrand You should not use VONVENDI if you: I use VONVENDI? von Willebrand Disease? disease learn to infuse VONVENDI by themselves or with the •You Are allergic to any ingredients in VONVENDI. should tell your healthcare provider if you: Consult your healthcare provider to make sure you are help of awith family member. • Are tohad mice ormedical hamsters. carefully bloodright testsaway to measure levels of von Haveallergic or have any problems. Call yourmonitored healthcarewith provider if your bleeding does Willebrand factor and factor VIII so they are right for you. Tell your healthcare provider if you are pregnant or • Take any medicines, including prescription and not stop after taking VONVENDI. breastfeeding because VONVENDI not be right for you. You may infuse VONVENDI at a hemophilia treatment non-prescription medicines, suchmay as over-the-counter Medicines are sometimes prescribed for purposes othercenter than (HTC), at your healthcare provider’s office or in your home. medicines, supplements or herbal remedies. those listed here. Do not use VONVENDI for a condition for You should beprescribed. trained on Do how toshare do infusions by your What I tell including my healthcare • Haveshould any allergies, allergies provider to mice or before hamsters. which it is not not VONVENDI with other healthcare provider or HTC. Many symptoms people with von Willebrand I• use people, even if they have the same that you have. Are VONVENDI? breastfeeding. It is not known if VONVENDI passes into disease learn to infuse VONVENDI by themselves or with the You should healthcare provider your milktell andyour if it can harm your baby.if you: help of a family member. The risk information provided here is not comprehensive. To • Have or have or hadplanning any medical problems. Are pregnant to become pregnant. It is not Call your healthcare right away if your bleeding does learn more, talk withprovider your healthcare provider or pharmacist known if VONVENDI can harmprescription your unbornand baby. • Take any medicines, including not stop after taking about Vonvendi. TheVONVENDI. FDA approved product labeling can be medicines, as over-the-counter • non-prescription Have been told that you havesuch inhibitors to von Willebrand Medicines are sometimes prescribed for purposes other than found at https:\\www.shirecontent.com/ PI/PDFs/ medicines, supplements or herbal remedies. factor (because VONVENDI may not work for you). those listed here. Do not useor VONVENDI for a condition for VONVENDI_USA_ENG.pdf call 1-800-828-2088. • Have any to to mice or hamsters. beenallergies, told thatincluding you haveallergies inhibitors blood which it is not prescribed. Do not share VONVENDI with other You are encouraged to report negative side effects coagulation factor ItVIII. people, even if they have symptoms that you have. • Are breastfeeding. is not known if VONVENDI passes into of prescription drugs to the the same FDA. Visit your milk and if it can harm your baby. www.fda.gov/medwatch, or call 1-800-FDA-1088. The risk information provided here is not comprehensive. To What is the most important information • Are pregnant or planning to become pregnant. IItneed is not to learn more, talkTakeda with your healthcareCompany providerLimited. or pharmacist know about VONVENDI? known if VONVENDI can harm your unborn baby. Copyright ©2019 Pharmaceutical 300 about Vonvendi. The FDA approved product labeling can be Shire Way, Lexington, MA 02421. 1-800-828-2088. VONVENDI can cause clots particularly in patients with • Have been told that blood you have inhibitors to von Willebrand found https:\\www.shirecontent.com/ PI/PDFs/ All rightsatreserved. known factors VONVENDI for blood clots. this with your factorrisk (because mayDiscuss not work forrisk you). VONVENDI_USA_ENG.pdf or call 1-800-828-2088. healthcare provider. • Have been told that you have inhibitors to blood TAKEDA and the TAKEDA logo are negative trademarksside or registered You are encouraged to report effects tradeYou can have allergic reactions to VONVENDI. Symptoms may coagulation factor VIII. marks of Takeda Pharmaceutical Company Limited. of prescription drugs to the FDA. Visit include generalized itching; rash or hives; rapid swelling of the VONVENDI is a registered trademark Baxalta Incorporated, www.fda.gov/medwatch, or call of 1-800-FDA-1088. skin or mucous membranes; chest pain or tightness; tightness

What is the most important information I need to of the throat; low blood pressure; shock; drowsiness; nausea; know about VONVENDI? vomiting; tingling, prickling, burning, or numbness of the skin;

VONVENDI cause blood particularly in patients with restlessness;can wheezing and/orclots diﬃculty breathing; known risk factorsdizziness; for bloodorclots. Discuss this risk with your lightheadedness; fainting. If symptoms occur, healthcare provider. immediately and get emergency stop using VONVENDI treatment rightallergic away. reactions to VONVENDI. Symptoms may You can have include generalized itching; rash or hives; rapidfactor swelling of the Your body can form inhibitors to von Willebrand or factor skin An or inhibitor mucous is membranes; chest pain or tightness; tightness VIII. part of the body’s normal defense system. ofyou the form throat; low blood drowsiness; If inhibitors, theypressure; may stopshock; VONVENDI or FVIIInausea; from vomiting; tingling, prickling, burning, or numbness of the working properly. Consult with your healthcare provider to skin; make restlessness; wheezing and/or diﬃculty breathing; sure you are carefully monitored with blood tests for the lightheadedness; dizziness; fainting. If symptoms development of inhibitors to or von Willebrand factor or occur, factor VIII. stop using VONVENDI immediately and get emergency treatment right away. Your body can form inhibitors to von Willebrand factor or factor VIII. An inhibitor is part of the body’s normal defense system. If you form inhibitors, they may stop VONVENDI or FVIII from working properly. Consult with your healthcare provider to make sure you are carefully monitored with blood tests for the development of inhibitors to von Willebrand factor or factor VIII.

a Takeda company.

Copyright ©2019 Takeda Pharmaceutical Company Limited. 300 Issued 02/2019 Shire Way, Lexington, MA 02421. 1-800-828-2088. S48947 All rights 06/19 reserved. TAKEDA and the TAKEDA logo are trademarks or registered trademarks of Takeda Pharmaceutical Company Limited. VONVENDI is a registered trademark of Baxalta Incorporated, a Takeda company. Issued 02/2019 S48947 06/19

Copyright ©2020 Takeda Pharmaceutical Company Limited. 300 Shire Way, Lexington, MA 02421. 1-800-828-2088. All rights reserved. TAKEDA and the TAKEDA logo are trademarks or registered trademarks of Takeda Pharmaceutical Company Limited. VONVENDI is a registered trademark of Baxalta Incorporated, a Takeda company. US-VON-0055v1.0 05/20

What's the difference?

by Janet Brewer, M.Ed

HES was founded to develop and share comprehensive health care education for rare disorders. As the needs

and wants of the community evolved, we found we could not provide all the essential aspects required by the communities we served like travel request scholarships and hardship grants. Thus, nSpiration, was founded to assist those in need. Please read on to find out more about the differences.

Since 2009, CHES (Comprehensive Health Education Services) has proudly served the educational needs for members of the bleeding disorder community. Our focus has traditionally been on those with inhibitors, rare bleeding disorders, and women with any bleeding disorder. We have deeply personal connections with members of these communities. As owners, Eric Lowe and Janet Brewer have intimate knowledge of what it means to live with inhibitors, vWD, women with bleeding disorders and dear friends with rare bleeding disorders. Over the years, with support from grants and sponsorships, CHES created five (5) programs for the inhibitor community and this publication, LifeLines for Health. In addition, we created two (2) programs for rare bleeding disorders, FVII and Glanzmann’s Thrombasthenia (GT) and the LadyBugs program for women affected by bleeding disorders. Since 2017, we have been honored to work with physician researcher, Dr. Diane Nugent to facilitate molecular sequencing to determine specific variants for FVII and GT (2019) at our programs. In 2019, we partnered with Drs. Joanna Davis, Fernando Corrales-Medina and Kelli Fraga to assess joint arthropathy via ultrasound in women with factor disorders at the LadyBugs Program. These studies have yielded poster abstracts at WFH, ISTH and THSNA. None of these programs would have been possible without the support of these fabulous patient communities. It is their input, their needs, their voices that grew these programs to what they are today. We at CHES remain deeply blessed with these trusted relationships that have grown and developed over the years.

LIFELINES for HEALTH

Spring/Summer 2021

We happily donated monies to families who were experiencing economic hardship or funds to attend national meetings. Our participants would frequently ask us if they could make donations to CHES, which were not tax deductible as a for profit company. As funding resources became more and more challenged, we streamlined programs. We listened to our participants who told us "you need to start a non-profit so we can contribute to keep these programs that are invaluable to our family. We can’t find this level of support anywhere. Our lives have been changed because of CHES."

nSpiration was founded because of YOU, our families. Its mission is to provide assistance and access to individuals and families affected by rare chronic conditions at a national level. nSpiration accomplishes this by fundraising to create travel scholarships for individuals and families to attend national meetings where specialists present on the latest treatment updates and communities are developed to lessen the isolation. Rare disorder communities are often deeply impacted by financial hardship due to high medical costs, and/ or medical challenges that impact the ability to maintain steady employment. For many, financial ruin is one step away. As a philanthropic organization, nSpiration seeks to support your need for access to highly quality education, research, community support and financial assistance during difficult times. nSpiration is run by its own independent board of directors that volunteer their time to supports its mission. As a new non-profit, they contract with CHES for program development services due to their highly regarded

WHAT’S NEW?

reputation in the bleeding disorder community for quality educational experiences. CHES is proud to lend their expertise to other non-profits as a health education event management company focused on rare, chronic conditions.

were no travel expense support. As we prepare to plan late 2021 live event programs, with the economic hardships created by COVID, the need for travel expense support will no doubt be higher than ever.

In a 2020 survey of potential program participants, only 17% indicated that they would be able to attend if there

So How

can

YOU

Help?

DONATE Go to https://nspiration.foundation/, watch the video by Connie L. Montgomery about what nSpiration hosted programs have meant to her family and donate what you can. Encourage your family and friends to do the same.

FACEBOOOK FUNDRAISERS Super easy to set up whether you ask for donations to be made to nSpiration for your birthday or just because!

1) After logging into Facebook, search for "fundraiser"

3) Click "Select Nonprofit"and search for "nSpiration" to get started

LIFELINES for HEALTH

Spring/Summer 2021

2) Select Fundraisers on the right

SHOP AT AMAZON Are you an Amazon shopper (who isn’t in a pandemic)? Let Amazon do the donating for you by joining AmazonSmile. Amazon will donate 0.5% of eligible purchases to our non-profit nSpiration — no fees, no extra cost. It's quick and simple to setup.

Shopping on Computers 1) Visit Smile.Amazon.com 2) Sign into your Amazon account 3) Search for and select "nSpiration" as your charity of choice *IMPORTANT – You must always shop at Smile.Amazon.com (rather than Amazon.com) to support "nSpiration"

Smile.Amazon.com is is a sub-domain of Amazon, so you can shop with the same trust knowing no third-parties are involved.

Shopping on Smart Phones/Tablets (with app) 1) After clicking on the menu button on your Amazon app, go to Settings. 3) Select “Turn on AmazonSmile” and follow the prompts to complete.

2) Select AmazonSmile…

WHAT’S NEW?

Remembering...

by Barb Forss

Sarah Chan

arah Chan. From the moment I met her, there was something really special about her. I couldn’t really define it, but she was just so...cool. With everything going wrong in her life, health-wise, financially and emotionally, for some reason, she used it all, this "playground of life", to laugh at the down times, and help the rest of us rise to her level of happiness, and to see the humor in things first.

life. Maybe it was her very dry wit and self-effacing humor. Maybe it was her need to advocate for the Glanzmann’s Thrombasthenia Community. Or, for Women With Bleeding Disorders. Probably, it was all of the above. Sarah, for just the short time that I knew her, became my Daughter-FromAnother-Mother. I do know that after meeting Sarah for the first time, I just embraced her. She was that much fun to be around!

I actually envied her “matter-of-fact” take on being a severe bleeder. She was that amazing. And so funny! Mature beyond her youth. So very witty. Always wise-cracking with that peculiar kind of dark humor only those of us who live with chronic conditions can laugh at.

I never heard her complain, even when she was at her worst and she deserved to. In the short time I knew her, she lost both of her parents within a few months of each other. That “Mother” in me wanted to just hold and hug her forever, and let her know that we, the Bleeding Disorders Community, would be there for her any way we could. And you know what? We were! She inspired that in all who she met.

Maybe it’s because I struggled to have kids, and because of my undiagnosed FVIId, am now childless in my 70th year of

It was traumatic for many of us when we found out that Sarah lost her life-long, 28-year battle with Glanzmann’s Thrombasthenia, GT. She fought her hardest to live, and that silly side of her was still joking into the last few weeks of her life. When she had two falls a few days apart that caused some major bleeding, I told her I wanted to duct tape her to the wall to keep her safe. She replied, “Only if it’s next to the refrigerator!” Sarah, my Foodie Friend! Little did I know the meals we shared in Anaheim would be our last. In fact, our last messages to each other were about the trip she planned to visit me here in the Pacific NW and figuring out where we could find the best Asian bistros! But I choose now to celebrate our time together, and remember Sarah for her brains, charm, advocacy and inner beauty. God puts people into your life for a reason, and I think in my case with Sarah, it was to learn humility, patience and perseverance. And to laugh more than cry. Something she taught me. Our Community was blessed to know her. I can see her smiling eyes and cute button nose now, giggling as we think of her, in her very own “Aw, shucks" kind of way. Rest in Peace, Sweet Sarah Chan. Gone but not forgotten, with the lovely legacy of laughing at your troubles, that you imprinted on all of us.

LIFELINES for HEALTH

Spring/Summer 2021

COMMUNITY CHATTER

PROGRESS in the

Diagnosis Management of

vonWillebrand Disease V

on Willebrand Disease (VWD) is the most common inherited bleeding disorder with most patients experiencing bleeding from mucosal surfaces, such as nosebleeds, gingival bleeding, heavy menstrual periods, and easy bruising, as well as bleeding from trauma or with surgical procedures. Some individuals with more severe VWD may also have gastrointestinal bleeding and bleeding into muscles or joints. These symptoms are significant and impact day-to-day activities and overall quality of life. Around 0.1% of the population have symptoms and laboratory studies consistent with VWD, and unfortunately,

LIFELINES for HEALTH

Spring/Summer 2021

many individuals are undiagnosed and don’t seek medical attention for the bleeding they experience. Rather, they suffer with their bleeding symptoms throughout their lives thinking that what they experience is just their “normal”. Fortunately, in 2021 there has been progress in the diagnosis and management of VWD, with a unified directive from the scientific medical and patient advocacy organizations to improve awareness, diagnosis, treatment, and access to care for those individuals with VWD.

By: Jonathan C. Roberts, MD

VWD Laboratory Diagnosis and Current Limitations To begin understanding VWD, we need to take a step back to understand von Willebrand Factor (VWF) and its overall role in coagulation. VWF is a multimeric glycoprotein, composed of many monomers (identical protein pieces) that have binding sites for platelets, collagen, and factor VIII (FVIII). VWF is stored in granules called Weibel-Palade bodies in endothelial cells (cells that line blood vessels and tissues) and alpha granules in platelets. When injury to tissue occurs, VWF goes to the injury site and initially functions as sticky “platelet Velcro” to bind platelets and collagen and begin the process of forming a blood clot. After the platelets initially bind, they send signals to other platelets and ultimately stick more platelets to the injury site through platelet aggregation, forming an unstable platelet plug. After that, the second role of VWF comes into play as the chaperone transport of FVIII, taking it to the site of trauma. On the platelet plug surface, FVIII along with other coagulation factors propagate the coagulation cascade and ultimately form thrombin and subsequently a firm, fibrin cross-linked clot. If an individual lacks enough VWF in circulation, or if the VWF they make is dysfunctional, they are diagnosed as having VWD. Diagnosis of VWD has historically been challenging due to a number of factors. The first is that amount of VWF in circulation can vary due to stress, inflammation, exercise, blood type, and hormone fluctuations. Therefore, when an individual is tested, VWF levels may be falsely elevated and a clinician may “miss” VWD diagnosis if only testing VWF levels on one occurrence. This can be particularly difficult in crying children or those who are easily stressed with having their blood drawn for testing. Nevertheless, if an individual personally has excessive bleeding symptoms and VWF levels <50%, it is consistent with a diagnosis of VWD.

FEATURE

VWD Laboratory Diagnosis and Current Limitations (cont.) The next issue has been with the laboratory tests available for VWD diagnosis. Testing for the amount of VWF protein, called the VWF antigen (VWF:Ag) has been a relatively reliable laboratory test over the years with VWF:Ag levels more consistent from laboratory-to-laboratory and also within the same laboratory. However, the classic “gold standard” laboratory test for VWF activity (specifically platelet-binding activity), has been more problematic. The VWF ristocetin cofactor (VWF:RCo) test measures VWFplatelet binding activity through using an old (no longer clinically used) antibiotic, ristocetin. When ristocetin was in use as an antibiotic, it was noticed that patients would get platelet clumping and low platelets, which placed them at risk for bleeding. Coagulation laboratory scientists determined a method to use ristocetin to measure the VWF-platelet binding activity, and thus the VWF:RCo was developed. The drawback to VWF:RCo is that the laboratory test can vary up to 30% or more between

LIFELINES for HEALTH

Spring/Summer 2021

different laboratories and even vary within the same laboratory. Meaning that if an individual’s VWF:RCo was low and diagnostic for VWD (i.e. <50%) in one laboratory, it may not be in another, and even could vary significantly if retested in the same laboratory! As you may imagine, this has caused frustration and difficulty in VWD diagnosis for physicians and patients alike. Variability in a laboratory test for a protein that can have a variable level anyway based upon stress, inflammation, etc. makes refinement of VWD diagnosis challenging. Thankfully, we have a new VWF platelet-binding activity test that does not use ristocetin called VWF:GPIbM. This laboratory test measures the ability of VWF to bind platelets with similar accuracy as the VWF:Ag. However, a major continued drawback is that few laboratories in the U.S. have capabilities to perform VWF:GPIbM, therefore many laboratories are continuing to rely on VWF:RCo as a primary means of VWD diagnosis.

An additional important VWF activity is binding to collagen. Historically, testing VWF collagen-binding activity (VWF:CB) was not always completed as part of a laboratory evaluation for VWD. However, in the past few years, laboratory tests for VWF collagen-binding to types I, III, IV, and VI collagen have been developed and specific individuals affected with these VWF collagen-binding defects have been discovered. Therefore, there may be additional individuals, previously with negative laboratory evaluations for VWD, who were not tested for specific VWF collagen-binding defects and remained currently undiagnosed. Notwithstanding all these VWF laboratory tests just discussed, there are even more VWF activity tests to further evaluate VWF-FVIII binding, VWFplatelet binding, VWF structure with VWF multimer analysis, in addition to VWF genetic testing. The VWF laboratory testing process can be frustrating for patients and challenging for clinicians desiring to make an accurate and timely VWD diagnosis.

VWD Diagnosis - Types of VWD It is important to understand that VWF is a large, complex protein with many functions and that deficiencies in any of these functions can lead to a variety of subtypes of VWD. Type 1 A majority of individuals with VWD, around 80%, have type 1 VWD, which is characterized simply by lack of VWF. In general, individuals with VWF levels 30-50% have more mild bleeding symptoms, and bleeding symptom severity increases as VWF levels get 30% or lower. I commonly educate my type 1 VWD patients that they, “just don’t have enough platelet Velcro”, which leads to prolonged bleeding symptoms. Individuals with type 1 VWD have normally functioning VWF, but reduced levels. Type 2 and Subtypes To understand variant VWD, it is helpful to consider also how individual VWF monomers join together to make long multimers. Again, referring to the VWF-Velcro analogy, the VWF-Velcro needs to be long enough and sticky enough to function as it should. Variant VWD occurs when there is dysfunctional VWF. Type 2A VWD occurs with significantly dysfunctional VWF-platelet binding and usually significant lack of large VWF multimers. In type 2A VWD the VWF-Velcro is not long enough to stick to platelets effectively to the injury site. Type 2B VWD occurs when VWF-platelet binding is much too enhanced to the point that platelets can be consumed and individuals may have low platelet

counts, known as thrombocytopenia. In type 2B VWD, VWF multimers may also be too small. Type 2M VWD describes dysfunctional VWF-platelet or - collagen binding where VWF multimer size is normal. Type 2N VWD encompasses deficient VWF-FVIII binding and occasionally individuals will be misdiagnosed as mild hemophilia A (factor VIII deficiency). It is important to distinguish type 2N VWD from mild hemophilia A as the clotting factor deficiencies and treatments are different (VWF vs FVIII replacement). Type 1C VWD describes those individuals with normally functioning VWF, but increased VWF clearance. For example, these individuals may not be able to utilize desmopressin (DDAVP) because the VWF they release from cellular stores is rapidly cleared from circulation. Type 3 Type 3 VWD is the most severe form and is characterized by near or complete absence of VWF. Individuals with type 3 VWD usually have a more straightforward diagnosis because VWF will most certainly be lacking with any VWF laboratory tests performed. Type 3 VWD bleeding is typically more severe, and patients may experience more severe bleeding such as muscle and joint bleeds, as well as gastrointestinal bleeding.

FEATURE

Improvements in VWD Diagnosis When considering the challenges with VWD diagnosis, the many different VWD subtypes, and needs for diagnostic improvements, physician scientists and coagulation researchers have endeavored to make improvements to VWD diagnostic laboratory tests. One such improvement is the VWF:GPIbM as previously discussed. Another new VWD laboratory test is the VWF Multiplex Activity Assay (VWF-MAA), developed by colleagues at the BloodCenter of WI and myself.

LIFELINES for HEALTH

Spring/Summer 2021

The VWF-MAA is unique in that it takes some of the VWF activity tests previously described and analyzes VWF and its activities on one laboratory testing platform. Specifically, it tests the VWF:Ag, VWF:GPIbM, VWF-FVIII binding, VWFcollagen binding, and VWF propeptide (a test to evaluate VWF clearance) on one unified testing “strip” platform. The VWF-MAA uses a well-established testing platform called an enzyme-linked immunosorbent assay (ELISA), which is widely available in most clinical laboratories. In theory, this VWF-MAA could be used throughout the US and internationally, and it may be lower in cost as it is one, unified testing methodology rather than multiple, individual VWF activity tests.

In the initial study describing the laboratory test’s development, the VWF-MAA was >88% accurate in discriminating variant VWD from a cohort of known VWD patients. A follow-up investigation reported this year at the Hemostasis & Thrombosis Research Society 2021 Scientific Symposium, showed that the VWF-MAA could be used as a screening test in previously undiagnosed patients to accurately determine type 1 VWD, variant VWD, or individuals without VWD with an overall accuracy of >72%. It is exciting to be a part of improving the diagnosis of VWD, and hopefully the VWF-MAA will allow for more rapid, accurate diagnosis to improve the care of individuals with VWD. If individuals with or without VWD are interested in being tested on the VWF-MAA, it is currently only available as a research test, but may be utilized in some of the national collaborative studies such as those by the American Thrombosis & Hemostasis Network (ATHN) or others being done through your local, federally recognized, bleeding disorders hemophilia treatment center (HTC).

FEATURE

The ASH ISTH NHF WFH 2021 Guidelines on the Diagnosis and Management of VWD This year also marks an important landmark in the publication of the updated, evidence-based VWD guidelines from the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation of Hemophilia (WFH). This huge undertaking involved the establishment of a multidisciplinary guideline panel including 4 patient representatives to review the medical literature and evaluate patient and clinician prioritized clinical questions to refine the diagnosis and management of VWD. The guideline-development panel provided clarity on many important topics regarding VWD.

2021 VWD DIAGNOSTIC Guidelines Key Recommendations There were 11 sound, evidence-based recommendations made by the review panel regarding VWD diagnosis, and the following are some highlights of the recommendations made. I would encourage those interested to review the full clinical guidelines freely available from the journal, Blood Advances. The first key recommendation is in regard to the role of bleeding-assessment tools (BATs) in the assessment of patients suspected of VWD. There have been many iterations of BATs over the years, with the ISTH-BAT as one of the more widely used and straightforward to administer. These standardized bleeding questionnaires capture the bleeding an individual has experienced throughout their lifetime, and significant bleeding events lead to the calculation of a bleeding score. The higher the score, the more bleeding symptoms, and a positive bleeding score using a validated BAT suggests an individual should undergo specific

LIFELINES for HEALTH

Spring/Summer 2021

laboratory testing to evaluate for a bleeding disorder. The guideline panel specifically recommends using BATs as an initial screening test for those seen in the primary care setting, as opposed to those referred to a hematologist. The next key recommendations are in regard to specific diagnostic assays and laboratory cutoffs for type 1 and type 2 VWD. A useful diagnostic algorithm was produced as a guide for clinicians involved in the diagnosis of VWD, and though it describes a complex process, it provides a well-thought, unified approach using the currently available VWF diagnostic laboratory assays. A highlight diagnostic recommendation is in regard to the true diagnosis of type 1 VWD. As we have seen, VWF is a complex molecule with difficulty pinning-down the true baseline level in an individual. The guideline panel recommends a VWF level <30% regardless of bleeding, and a VWF level <50% in patients with abnormal bleeding to confirm type 1 VWD diagnosis.

These recommendations come from recent, sound evidence demonstrating that individuals in the VWF levels of 30-50% with abnormal bleeding may experience excessive bleeding symptoms from VWF level alone, thus consistent with the diagnosis of VWD. This increase in diagnostic level from a strict VWF level <30% considers new understanding in the variability in patient VWF levels, available laboratory assays, and relation to individual abnormal bleeding symptoms. This is important for the patient community, because it allows for improved utilization of VWD therapies, improving ability for treatment, and overall hopeful improvements in quality of life and management of bleeding symptoms. Another key recommendation is in regard to type 1 VWD patients whose VWF levels may normalize over time. It has been increasingly recognized that individuals with historic diagnosis of type 1 VWD may now have levels that have normalized as they age. In general, it is thought that VWF levels may increase ~1-2% for every decade of life. For those with mildly low historical VWF levels, if retested, VWF levels may now be >50%. What is less well-understood is if the VWF level increase reliably leads to improvement in bleeding symptoms. Due to the complexities of VWF previously described, it is not a clear answer if individuals should

be “un-diagnosed” with VWD. It is known that aging and development of other comorbidities can increase measured VWF levels; however, those increase VWF levels and relation to presence and severity of bleeding symptoms is not well-established. Therefore, the guideline panel suggests reconsidering the diagnosis as opposed to removing the diagnosis of patients with historic type 1 VWD who now have VWF levels that have normalized with age.

The VWD Diagnostic and Treatment Recommendations can be read in its entirety at: https:// ashpublications.org/bloodadvances/ article/5/1/280/474888/ASH-ISTHNHF-WFH-2021-guidelines-on-thediagnosis?searchresult=1

FEATURE

2021 VWD MANAGEMENT Guidelines Key Recommendations There were 12 sound, evidence-based recommendations made by the review panel regarding VWD management, and the following are some highlights of the recommendations made. Again, I would encourage those interested to review the full clinical guidelines freely available from the journal, Blood Advances. The first key recommendation in regard to VWD management (that I am personally most excited about) is the formal recommendation to suggest prophylaxis for severe, frequent recurrent bleeding. Prophylaxis (treatment to prevent bleeding rather than only treating bleeding on demand) has been a longstanding recommendation for hemophilia management. The difficulty with implementing this recommendation in VWD is that the bleeding type and severity can vary widely among individuals and there has been lack of robust evidence for prophylaxis in VWD. However, intuitively prophylaxis makes sense for individuals with excessive bleeding and some patients and clinicians have adopted some form of prophylaxis in VWD prior to these formal recommendations. Prophylaxis in VWD may be a new concept for some, and certainly performing intravenous administration of VWF concentrate (if indicated) can be challenging from a lifestyle and technical skill standpoint. Other treatment options besides VWF concentrate include antifibrinolytics, desmopressin, and hormonal therapy for excessive menstrual bleeding. Thankfully, local HTCs are well-equipped to be an ally for individuals with VWD and tailor a treatment program to

meet their needs and improve their quality of life. When considering prophylaxis, the guideline panel also suggests that bleeding symptoms and specific need for prophylaxis should be periodically reassessed and to determine its specific utility in an individual. For example, some women with heavy menstrual bleeding may only require prophylaxis immediately prior to and during their menstrual period, or an individual with severe nosebleeds may only require preventative treatment during the winter months when they are more prone to bleeding events.

Another key recommendation entails recommendations for anticoagulation in patients with VWD and cardiovascular disease where antiplatelet or anticoagulation therapy is otherwise indicated. As individuals with VWD and other bleeding disorders now live longer with normal life expectancies, risks for clotting events can also develop. A challenge for patients and clinicians is to balance the clotting risk with the bleeding risk, and the guideline panel highlights the importance of reassessing the bleeding risk throughout the course of treatment. Certainly, in hemophilia, there are individuals who receive treatments for preventing bleeding while also taking antiplatelet and anticoagulation therapies. Individuals with VWD are no different in that regard, and again stresses the importance of management in collaboration with a bleeding disorder HTC.

LIFELINES for HEALTH

Spring/Summer 2021

Other key recommendations for optimal management of VWD involve recommended target FVIII and VWF activity levels for clinicians in regard to major surgeries, minor surgeries, other invasive procedures, as well as management options for excessive menstrual bleeding and management during labor and delivery, and in the postpartum time period. The suggested use of antifibrinolytics in postpartum bleeding management with emphasis on the safety in breastfeeding highlights an additional benefit of adjunctive hemostatic agent use in VWD.

Conclusions In summary, there has been much progress in the diagnosis and management of VWD in 2021. Unified national and international society, physician scientist, and coagulation researcher commitments to enhancing awareness, diagnostic methodologies, treatment strategies, and patient-centric care have begun to further strengthen the bleeding disorder community and enhance lives of individuals and families with VWD. I am hopeful that our current successes will only fortify our resolve and dedication to those living with VWD, and motivate future investigations and improvements for years to come.

Jonathan C. Roberts, MD is the Associate Medical Director and Associate Research Director at the Bleeding & Clotting Disorders Institute (BCDI) and Assistant Professor of Pediatrics at the University of Illinois College of Medicine at Peoria in Peoria, IL, USA. Dr. Roberts’ research areas of interest are in advancing novel laboratory assay development to improve the diagnosis of von Willebrand Disease and to enhance individualized clinical management of hemophilia. He has received numerous young investigator research awards, has over 40 peer-reviewed research publications and abstracts, and has had grant funding from the NHF, WFH, and NIH among others. Dr. Roberts has a personal passion for the bleeding disorders community as he is also an individual with severe hemophilia A.

FEATURE

Exploring the science behind gene therapy research Gene therapy research has the potential to bring an entirely new option to people with specific genetic conditions. Many gene therapies are in clinical trials to evaluate the possible risks and benefits for a range of conditions, including hemophilia. HemDifferently is here with gene therapy education, providing accurate information on the basics and beyond. What questions do you have? Get them answered. Explore gene therapy at HemDifferently.com.

No gene therapies for hemophilia have been approved for use or determined to be safe or effective.

THE 5 STEPS OF INVESTIGATIONAL GENE TRANSFER One method of gene therapy currently being explored in clinical trials is called gene transfer. This approach aims to introduce a working gene into the body to determine if it can produce a needed protein.

STEP 1 CREATING A WORKING GENE A working copy of a mutated gene is created in a laboratory.

STEP 2 BUILDING A THERAPEUTIC VECTOR A therapeutic vector is used to protect the working gene and serves as a transport vehicle for the gene to enter the body. The therapeutic vector is created from a neutralized virus, meaning no viral genes remain inside.

STEP 3 DELIVERING THE WORKING GENE A single, one-time infusion delivers large numbers of therapeutic vectors into the body.

STEP 4 MAKING PROTEINS Once in the body, the new working gene is designed to provide instructions for the body to make the protein it needs on its own. =Proteins.

STEP 5 MONITORING AND MANAGING HEALTH Clinical trial participants are regularly monitored to better understand the safety of the gene transfer and to evaluate its effect on the body.

Emerging Advocates Could 'Sway' Copayment Accumulator

BATTLE

By: Gwen Cooper, CEO, Patient Services Incorporated James Romano, Care & Cure Partners

brief pause in one insurance providers copayment accumulator program provides a window of opportunity for patient advocate groups to stop the practice at the state level throughout the country.

2021 dawned with patient advocates scoring a temporary victory via the United HealthCare announcement of a moratorium on the inclusion of copayment accumulators in the benefit design of their plans. While United Healthcare has stepped back, many health insurance providers have moved forward, implementing this policy and other mitigation strategies. The ultimate consequence of these actions is additional costs for families struggling with rare diseases and chronic illnesses. With over 16 million Americans losing their employer sponsored health insurance in 2020, now is not the time to expand these programs which prevent families from obtaining the health care they need.

LIFELINES for HEALTH

Spring/Summer 2021

While some more cautious health insurance plans are adopting a “wait & see approach,” we anticipate that in the coming months, the Biden Administration will either reaffirm or modify the existing policy. The Centers for Medicare and Medicaid Services (CMS) issued a preliminary rule prohibiting the practice of the copayment accumulators in the 2020 Notice of Benefit and Program Parameters in

federally regulated plans. However, CMS reversed course several months later, protecting the practice in the 2021 Notice. Because of the confusion from Federal Agencies, Congress introduced the Preserving Patient Savings on Drug Costs Act at the end of 2020, to place a moratorium on the rule taking affect until the Covid-19 pandemic has ended. This bipartisan legislation was introduced by Congressman Donald McEachin (D-VA) and Congressman Rodney Davis (R-IL). However, the jurisdiction of this legislation is limited to federally regulated plans. Unless the Biden Administration issues a rule change, copayment accumulators will continue to be included in commercial plans that are federally regulated. While patient advocates have pinned their hopes on a more pro-patient centered outlook coming out of the Biden Administration, that optimism may be premature. The previous Democratic administration promulgated numerous regulations very favorable to the health insurance industry, such as The Third-Party Payment of Qualified Health Plan Premiums Rule. As you may know, this rule allows health insurance providers to reject third party payments made to qualified health plans by all except government entities. Since the passage of The Affordable Care Act (Public Law 111-148), patients with rare and chronic illnesses have

been caught between the manufacturer that develops their treatment and the health insurance provider that offers the reimbursement strategy to pay for said treatment. Since the reform of the pre-existing condition exclusion, health insurance providers have developed new and inventive techniques to mitigate the influx of subscribers with rare and chronic conditions. One such technique is the copayment accumulator program. This practice specifically deals with copayment cards issued by manufacturers for brand named treatments and not copayment assistance provided by nonprofit charitable assistance organizations such as Patient Services Incorporated (PSI). However, if successful, insurance companies could expand the program to exclude copayment assistance programs offered by charitable organizations. In the case of Copay Accumulators, the insurance provider accepts the payment card but does not count the amount toward the out-of-pocket maximum. Thus, this mitigation practice makes the rest of the medical expenses of the family more expensive. In the United States, we place a high regard for the federal investment in the National Institutes of Health (NIH), which is funded at $27 billion for the current fiscal year. This investment leads to the funding of investigator-initiated research that begins the path to the latest vaccine, cure, or next generation treatment. Landmark legislation, such as The Orphan Drug Act (Public Law 94-414) and The 21st Century Cures Act (Public Law 114-255), have been passed to create incentives to research treatments and cures. In the span of the last quarter century, research has cured Hepatitis C and Spinal Muscular Atrophy (SMA) in infants; brought the first treatments for Hereditary Angioedema & Idiopathic Pulmonary Fibrosis and have made HIV/AIDS a chronically treated condition rather than the death sentence of the decade prior. The reimbursement strategy often plays second fiddle to the primary task of developing the new and innovative therapy. And while the intent is to put these new and improved treatments in the hands of those who need them, strategies like copayment accumulators put a larger burden of the cost back on to the consumer.

WHAT’S NEW?

Public policy regarding copayment accumulators has been confused and jumbled on the federal and state levels. While the federal law hangs in the balance, at the state level we are witnessing patient advocates in multiple states working together to end the abuses of the copayment accumulator. These advocates have stood up to health insurance providers to advance changes to this practice in state legislatures. Patient Services Incorporated is working with these patient advocacy leaders in many of these states to ensure access for patients with rare diseases and chronic illnesses to needed treatments and therapies. Five state legislatures have passed bans on the copayment accumulator programs. Those states are Arizona, Georgia, Illinois, Virginia, and West Virginia.

Committed to serving the needs of the rare bleeding disorders community and physicians

About Catalyst Biosciences, the Protease Medicines company Catalyst Biosciences is a research and clinical development biopharmaceutical company focused on addressing unmet medical needs in rare disorders of the complement and coagulation systems. Our protease engineering platform has generated two late-stage clinical programs, including marzeptacog alfa (activated) (MarzAA) and dalcinonacog alfa (DalcA). MarzAA is a next-generation subcutaneous (SQ) FVIIa that is entering an international Phase 3 registration trial (MAA-304; Crimson 1) for treatment of episodic bleeding in patients with Hemophilia A or B with inhibitors. We have initiated a Phase 1/2 trial of MarzAA in individuals with Factor VII deficiency or Glanzmann thrombasthenia, and in individuals with Hemophilia A receiving Hemlibra prophylactically. The phase 2 portion will treat episodic bleeding.

Pipeline

DalcA is a next-generation SQ Factor IX drug for the prophylactic treatment of individuals with Hemophilia B that has shown efficacy and safety in a Phase 2b clinical trial. We have a discovery stage Factor IX gene therapy construct – CB 2679d-GT – for Hemophilia B, that has demonstrated superiority compared with the Padua variant in preclinical models. Our complement pipeline includes a pre-clinical program partnered with Biogen for dry age-related macular degeneration, an improved complement factor I (CFI) protease for SQ replacement therapy in patients with CFI deficiency, and C4b-degraders designed to target disorders of the classical complement pathway, as well as other complement programs in development.

catalystbiosciences.com

This legislation protects access to both copayment cards issued by manufacturers in commercial insurance plans as well as copayment assistance provided by nonprofit organizations. Because of the success patient advocates have had, the number of states where copayment accumulator legislation has been introduced exploded in 2021—with approximately 20 additional states. Those states include California, Texas, New Mexico, Tennessee,

Rhode Island, Wisconsin, Alabama, Oklahoma, Kentucky, Ohio, Nebraska, Michigan, Florida, Maryland, Pennsylvania, and Oregon. With the economic damage wrought by the Covid-19 pandemic, now is not the time to limit a person’s ability to access treatments and therapies with “mitigation” schemes, whose true purpose is to exclude the individual from coverage.

Concerning statistics in 2020.

Patients did not purchase a prescription due to the cost

Patients were unable to access medication without some sort of financial assistance

Patients with chronic health conditions have not been able to afford out-ofpocket medical expenses

By allowing insurance companies to enact these copayment accumulators, policymakers will be continuing these trends. While United Healthcare and many other insurance providers are taking a “wait and see” approach to the Biden Administration, patient advocates are standing up and pushing for reform. If you live in a state where there is a bill active, we urge you to reach out to your State

Representative and State Senator to voice your support for banning this process. We all need to work together to ensure all Americans have access to the treatments and therapies they need to live the lives they deserve. Our friends and family members worry about their future fighting their illness; why make them worry about affording the treatments for the fight?

References 1.

Commonwealth Fund, Blog: Update: How Many Americans Have Lost Jobs with Employer Health Coverage During the Pandemic?” January 2021

2. CNBC, “Americans are skipping medically necessary prescriptions because of the cost.” February 2020 3. National Hemophilia Foundation, “National Registered Voter Sentiment on Patient Copay Assistance Programs.” October 2020 4. National Hemophilia Foundation, “National Registered Voter Sentiment on Patient Copay Assistance Programs.” October 2020

LIFELINES for HEALTH

Spring/Summer 2021

WHAT’S NEW?

Complimentary

By: Angela Lambing, MSN, ANP, GNP

Alternative

...Uses in Pain for Bleeding Disorders Part 3 This is the third and final installment in the review of complimentary pain management therapy reviewing the available research for persons with bleeding disorders.

Therapies included in this domain are:

n the first installment, the definition of complementary and alternative therapy (CAM) was reviewed as well as the mind body modalities available. The second domain under review was the Manipulative and Bodybased practices. The last 2 domains of CAM include natural products and energy therapies.

Natural Products •

Remedies

•

Botanicals

•

Potions

•

Vitamins

•

Oils

•

Minerals

•

Herbs

•

Probiotics

Historically, natural products have been used since ancient times and in folklore for the treatment of diseases and illnesses, where many products have gone on to become drug candidates. The use of natural products includes remedies, potions and oils with many of these bioactive natural products still being unidentified 1. This group also includes a variety of products, such as herbs (also known as botanicals), vitamins and minerals, and probiotics 2. It is important to note that these types of products are not FDA monitored in the same way as traditional medications, thus accurate dosages, drug-drug interactions, risks and benefits may be lacking.

LIFELINES for HEALTH

Spring/Summer 2021

Currently there is no research using herbal therapies for pain management in persons with bleeding disorders. One major concern - many people with bleeding disorders ingesting herbal therapies have the potential for increased bleeding risk. Several university hospital websites have listed herbal products that are known to increase bleeding risk and are listed in Table 1 3, 4 although this list may not be complete. If you are considering any of these products, it is important to have a discussion with your treatment center to review the risk/benefit profile. Further research with pharmacists’ input can be helpful, as they access websites that provide further medical information with botanicals. Essential oils are also included in the domain of natural products. The definition of an essential oil is a class of volatile oils that give plants their characteristic odors and

are used especially in perfumes and flavorings, and for aromatherapy 5.

There has been no clinical research with persons with bleeding disorders and the use of essential oils. Vicol et a. 6 discussed the use of aromatherapy to manage side effects of HIV; some of these patients also had hemophilia. Table 2 provides a list of Essential oils that have been reported to be helpful in pain management, although there is currently no data with respect to increased potential for bleeding in persons with bleeding disorders 7.

TABLE 1: Herbal Therapies for pain management that may increase bleeding risk (*nonexhaustive list) 3, 4 1. Angelica

11. Fish oil

21. Red clover

25. White willow

2. Aniseed

12. Ganoderma

22. St. John’s Wort

26. Willow

3. Black cohosh

13. Garlic

23. Turmeric (curcuma)

27. Zinc

4. Bromelain

14. Ginger

24. Vitamin E

5. Butcher’s broom root

15. Ginkgo

6. Cat’s claw

16. Ginseng

7. Chamomile

17. Glucosamine

8. Chondroitin

18. Horse chestnut

1. Lavender

4. Eucalyptus

7. Ginger

9. Fenugreek

19. Licorice

2. Rosemary

5. Cloves

8. Feverfew

10. Feverfew

20. Omega 3

3. Peppermint

6. Capsaicin

9. Turmeric

TABLE 2: Essential oils reported helpful in pain management

WHAT’S NEW?

The final domain in CAM therapy is Energy therapies defined as: A Therapies included in this domain are: form of CAM based on the belief that a vital energy flows through the human body. The goal of energy therapy is to balance the energy flow in the patient. It is used to reduce stress and anxiety and promote well-being 8. These therapies include: therapeutic touch, reiki, and Energy prayer. Therapeutic touch involves a practice derived from an ancient Therapies technique called laying on of hands. It is based on the premise that it is the healing force of the therapist that affects the patient's recovery; • Touch healing is promoted when the body's energies are in balance; and, by passing their hands over the patient, healers can identify energy • Reiki imbalances 9. Reiki a healing technique based on the principle that • Prayer the reiki master can channel energy into the patient by means of touch, using a spiritually guided life force energy 10. Therapists are specially trained and certified to perform these therapies. Currently there is no clinical research in these areas in persons with bleeding disorders. There are a few references to these therapies in the literature as case reports. The Hemophilia of Georgia blog reported the use of Reiki in a person with hemophilia to assist with back pain following a car accident 11. Krug et al. 12 reported a case of therapeutic touch use in a person with hemophilia and hepatitis C. The therapy was used to relieve fatigue and pain related to hepatitis. Fish documented the use of reiki and therapeutic touch in the care of HIV/AIDS patients, some with hemophilia 13. Prayer and faith have been documented as methods of pain management in the National Pain study completed in 2012 where 21-29% of subjects reported the use of their faith to manage pain. There are currently no research studies that explore this modality.

Summary Persons with a bleeding disorder (PWBD) experience pain in a variety of ways, whether it is acute pain related to a bleed or IV access to chronic pain, as a result of end stage joint disease. People are looking more toward the use of CAM therapy as alternatives to oral pain medicine particularly in the current climate of the opioid epidemic where access to appropriate pain medications are limited due to its misuse. CAM therapies have been well documented in other disease states suggesting their effectiveness for pain management. As reported, there remains opportunities for clinical research with the use of CAM in PWBD, thus providing evidenced based results to support the use of these therapies. Pain is a personal experience, and the management of pain also remains a

LIFELINES for HEALTH

Spring/Summer 2021

personal experience, as what may work for one person in their quest for pain relief may not work for another. As the PWBD travel through their pain experience, it is important for everyone to have frank discussions with their treatment provider to explore what may be helpful to them, reviewing risks and benefits and potential for increased bleeding risk. The use of supplemental factor use prior to many of these therapies may be needed. The National Hemophilia Foundation (NHF) provides resources to enhance the discussion with providers regarding pain management 15 and provide a hemophilia nurses’ guide to manage pain 16. The Hemophilia Federation of America (HFA) also provides patients with a tool kit to assist with pain management 17.

References 1. Dias D et al. A historical overview of natural products in drug discovery. Metabolites. 2012; 2; 303-36.

10. Definition of Reiki. Retrieved from: https://iarp.org/ learn-about-reiki/

2. Definition of natural products retrieved from: https://www.nccih.nih.gov/health/complementaryalternative-or-integrative-health-whats-in-a-name

11. Using reiki for pain relief and stress management. Blog: Hemophilia of Georgia. June 4, 2012. Retrieved from: https://www.hog.org/blog/detail/using-reiki-forpain-relief-and-stress-management

3. Herbal therapies with potential bleeding risk. Retrieved from: https://www.google.com/ search?rlz=1C1CHBF_enCA893CA894&biw=1205&bih =566&sxsrf=ALeKk00HhVOeMj75ML0NtTB9aWtlIlQS Tg%3A1585598440254&ei=6E-CXtOKD8W0tAbksI7Q CQ&q=herbal+therapies+%2B+hemophilia&oq=herbal +therapies+%2B+hemophilia&gs_lcp=CgZwc3ktYWIQ AzoECAAQRzoECAAQQzoFCAAQgwE6AggAOgQIIxAn OgUIABCRAjoHCAAQgwEQQzoICAAQgwEQkQI6Bwg AEBQQhwI6BAgAEAo6BggAEBYQHjoFCCEQoAE6CAg hEBYQHRAeUNqPJ1i-tydgsLgnaAJwAXgAgAHKAYgB6 RmSAQcxNC4xNi4xmAEAoAEBqgEHZ3dzLXdpeg&scl ient=psy-ab&ved=0ahUKEwjTnqa-_sLoAhVFGs0KHW SYA5oQ4dUDCAs&uact=5 4. University of Iowa. Herbal therapies with potential bleeding risk. Retrieved from: https://uihc.org/ health-topics/bleeding-disorders-and-naturalherbalmedicines 5. Definition of essential oil. Retrieved from: https:// www.merriam-webster.com/dictionary/essential%20 oil 6. Vicol MC. Alternative and traditional healing. Mental Health Practitioner’s Guide to HIV/AIDS. New York; Springer. 2013. 91-94. 7. Essential oils for pain management. Retrieved from: https://www.medicalnewstoday.com/articles/324572 8. Definition of energy therapy. Retrieved from: https:// www.cancer.gov/publications/dictionaries/cancerterms/def/energy-therapy

12. Krug P et al. Energy dialogue technique in healing and health: Relieving side effects and thyroid dysfunction in a male with haemophilia receiving PEGylated interferon and ribavirin treatment for hepatitis C virus – an anecdotal case study. Journal Holistic Nursing. 2013; 31(3): 204-13. 13. Fish DG. HIV and AIDs. The art and science of palliative care. 1st edition. 2014. AME publishing. 8796. Retrieved from: http://fp.amegroups.cn/cms/1dfe4 c6ad2ec84424ca5e9517ea330fb.pdf#page=107 14. Witkop M et al. A national study of pain in the bleeding disorders community: A description of haemophilia pain. Haemophilia. 2012; 18(3); 3115-9. 15. Baumann K & Panopoulos G. Communicating with your provider about pain. National Hemophilia Foundation. Retrieved from: https://www.hemophilia. org/node/9498 16. Witkop M, Lambing A, & Fritz R. Nurses Guide to Bleeding disorders. Chapter 18. Pain management. 2013. 1-35. Retrieved from: https://www.hemophilia. org/sites/default/files/document/files/Nurses-GuideChapter-18-Pain.pdf 17. Pain Tool Kit for Patients. Hemophilia Federation of America. Retrieved from: https://www.hemophiliafed. org/for-patient-families/resources/toolkits/paintoolkit-adults/

9. Definition of therapeutic touch. Retrieved from: https://www.medicinenet.com/script/main/art. asp?articlekey=33524

Angela Lambing has been a nurse for 40 years; 30 years as a nurse practitioner certified in adult primary care and geriatrics. She spent 15 years as the Henry Ford Hospital HTC nurse, responsible for all aspects of bleeding and thrombotic disorders. She is an expert in pain management in the bleeding disorders community, having completed many research projects in this area. She is widely published and has given talks on a variety of topics, locally, nationally, and internationally. Her last 5 years was spent as a clinical expert and educator for Bayer Health Care. She is now retired, but still focusing her energies and knowledge in the area of bleeding disorders. In the past few years, she has been one of many national experts on pain participating on the MASAC pain task force where she continues to provide support in this area.

WHAT’S NEW?

Validation Why You Need It. How To Ask For It. How To Give It.

LIFELINES for HEALTH

Spring/Summer 2021

by Dr. Gary McClain, PhD

ou may be familiar with the word validation. Or maybe not. It’s kind of a psychology word, one that therapists like me toss around. So, let’s start out with a definition of what validation means. I think the best way to define validation is through examples of what it means to feel validated: “You matter.” “You’re being heard.” “I care about you.” “You are appreciated.” Make sense? To be validated is having someone else acknowledge your essential humanity. Now, please allow me to explain more about validation, why you need it, how to ask for it, how to give it. And some encouragement: When people feel validated, the world feels a whole lot better.

What Does It Feel Like When We Aren’t Being Validated? Ever had the feeling you weren’t being validated? Here are a couple of examples of what that feeling is like. You may relate to what Abby and Tommy were experiencing.

Abby’s Story Abby was talking about her day with her husband, Ben. She told him about how she had handled a difficult situation at work. “I really took control here,” she said. And then she went on to describe a stress due to deadlines that needed to be met, and how she jumped in and helped organize the workflow to get the tasks completed on time. “I was the hero!” she exclaimed. Ben listened as she talked, and then smiled and said, “You always work well under pressure. Glad to hear you did it again.” And then Ben changed the subject. He had a couple of household finance concerns he wanted to discuss. “By the way,” Abby said, “It’s my turn to cook tomorrow night and I’m making that meat loaf you love so much.” “Please don’t,” Ben responded. “I really need to watch my weight.” At this point, Abby felt totally deflated, and she wasn’t sure why. The next morning, she called a friend during her break and told her about the conversation she had with Ben the night before. Her friend listened and then said:

FAMILY MATTERS

“It sounds like you needed some validation,” her friend said. “And why not? You have so much going on in your life. You work hard. You have a family to take care of. You have a bleeding disorder that you have to think about and often do something about. You’re trying to be a good mom. And some days are pretty rough for you, and you push ahead anyway. So why wouldn’t you want some validation for all of that once in a while?” Abby felt ashamed. “I know I’m appreciated by Ben and the kids, no doubt in my mind.” “Sure,” her friend answered. “But some days we just need to hear it.”

Tommy’s Story Tommy’s seventeen and living with a bleeding disorder. He’s come a long way in taking better care of himself. He’s been infusing himself for years. But he and his parents have had some conflicts here and there, mainly his parents trying

LIFELINES for HEALTH

Spring/Summer 2021

to set limits - not all that much different than what other parents go through with their teens. Of course, Tommy’s bleeding disorder causes his parents to be even more cautious. Like any teen, Tommy wants to be independent. Naturally, some disagreements have resulted. Tommy is taking good care of himself. He’s doing well in school. He’s being responsible, not taking risks with his health. And the disagreements with his parents aren’t happening nearly as often as they used to. Tommy is proud of himself for staying on the path, even when he didn’t feel like it. Last week, Tommy brought home the best report card he has had in a long time. When he showed it to his mom, she took a look and said, “that’s great.” His father said something similar: “I knew you had it in you.” Sure, his parents acknowledged his good grades. But that wasn’t what Tommy needed. What Tommy needed was for his parents to sit down with him and talk to him about the progress he has made. To tell him how proud they are that

he is staying one step ahead of his bleeding disorder. Maybe give him some examples of the changes he’s made, and how when he takes care of himself, that helps them, too. And to go over his grades with him, what he’s doing to keep his grades up, even the subjects he struggles with. To offer their support. Yes, in a word: validation. Tommy needed some validation from his parents. Like Abby, Tommy knows his parents love and care about him. But still, some days he just needs to hear it.

Needing Validation is Normal. We All Need to Feel Validated! What about you? Like Abby, if you’re living with a chronic condition like a bleeding disorder, you have a lot on your plate. And, also like Abby, a lot of what’s on your plate is what you do for other people, at work, and at home. It’s only human to want an “attaboy” or an “attagirl” once in awhile. Hearing your efforts for toughing it out during a rough time were actually noticed. Maybe with some encouragement. And like Tommy, if you’re going the extra mile to take good care of yourself, even on those days when that’s the last thing you feel like doing, it’s important to know that the people you care about recognize your efforts. Again, we all need some encouragement. Now, as you read these two examples, you may also have thought about times when someone in your life could have benefited from some validation from you, and you missed the opportunity to provide it. Yep, validation works both ways.

yourself. Self-talk is important to our mental health. Talk back to the critical voice. Make it a daily practice to give yourself the recognition you deserve: “Good work.” “You’re doing the best you can.” “You’ll make it happen. Just keep at it.” And do things that you enjoy, that keep you calm and centered, that enhance your well-being. Another great way to validate yourself. Review your foundation. What is your foundation? Your foundation includes your education, your skills, your past successes, your emotional support network, your health self-empowerment, your values, your personal qualities that contribute to your overall well-being. Take some time and make a list of all the many qualities that make up who you are. This is your foundation, and no matter how shaky the day feels, it is rock solid. Review the list whenever you need some validation.

We all need validation. On some days more than others. When you hit one of those days, here’s what you can do: Remember that validation starts from within. Therapists spend a lot of time talking with their clients about validation. My approach is always to start with helping my client to understand the ways in which they can validate themselves. We all need to be able to validate ourselves. This is the root of self-empowerment. So, validate yourself first. This is what I always say to my clients. Sure, we need to know that we aren’t invisible to the people we care about. But we have to be able to give ourselves recognition. That starts in your own mind, and what you say to

FAMILY MATTERS

Give yourself permission to need validation from others.

Asking for Validation

As I said, it’s human to need validation. But I talk to so many clients who feel they shouldn’t need validation. They have been told once too often that needing validation is being “whiny” or weak, or just plain needy. But it’s not. We all need to feel like the efforts we make in our daily lives are not just fading into the vapor, but that they are being noticed by others. And we want to hear they are noticing. A compliment and a little encouragement sure wouldn’t hurt either.

As I stated previously, it is only human to need validation. And when you do need to feel validated, it’s also okay to ask for it.

Ask yourself why you need validation and from whom. Be aware when you are feeling especially in need of validation. For example, is there something you did that was scary or difficult, and you want someone to acknowledge your success and what it took to achieve it? And is there a specific someone you most need to hear it from? Doing some self-exploration to understand this will mean that you are less likely to appear overly needy. In other words, get specific about who you need words of validation from.

Don’t beat around the bush. Ask. It’s always best to take the direct approach. If you have done your homework, so you know what you need and who you need it from, you will be more likely to speak with confidence and clarity. It’s as simple as: “I accomplished something today that I’m really proud of. It would mean a lot to me if you let me know you see how I am working hard to push through. I just need to hear it from you.” Or, “I know this isn’t a big deal but I made an effort to do this for you. I didn’t do it so that you would thank me, or pat me on the back, but I have to say it would be nice if you did.” Words, but also gestures. Just asking for a hug can be a great way to feel validated.

LIFELINES for HEALTH

Spring/Summer 2021

And keep in mind that your partner – and your children – may also need some validation.

Giving Validation at Home Living in a home where everybody feels validated is a home where everybody feels honored, cared for, respected.

One of the things I often hear from the partners of individuals living with a chronic condition like a bleeding disorder is that they don’t feel very validated, either. They talk to me about how they do everything they can to be supportive but don’t always feel like their efforts are appreciated, or even noticed. Validation works both ways. And when you give it, you may also experience more validation coming your way. If you have children, include them in these conversations, ask them what they need from you to feel validated. Create an environment of validation at home.

Here’s how to make your home a more validating place: Have a conversation about validation. You might want to sit down with your partner and talk about how they can encourage you. Be straightforward about what you need to be validated for. This could be both what you do for yourself to manage your bleeding disorder and what you do for the people around you. If you have children, include them in these conversations, and let them know what you need from them. If you are living with your parents, let them know what they can do to encourage you and make you feel validated.

Everyday, tell your kids how much they mean to you. Give them encouragement not only for successes, but for making the effort. Listen to them! Do the same for your partner. Set an example for your partner, set an example for your children. Give everyone in the household a chance to weigh in on family decisions. Encourage expressions of opinion, even if you disagree. Share your feelings and encourage family members to do the same. And support your children in exploring their interests, hobbies, and sense of personal style. Make it a daily practice to smile, share jokes, do acts of kindness, and give hugs. Lots of hugs.

Everybody is Special in their Own Way! It’s only human to need validation. So be clear when you need to feel validated. Look for ways to validate your partner and your children. Honor the specialness in everybody in your home. Honor each other for just being there. That’s teamwork!

Gary McClain, PhD is a therapist, patient advocate, and educator, specializing in helping clients deal with the emotional impact of chronic and life-threatening health conditions, as well as their families and professional caregivers. He works with them to understand and cope with their emotions, to learn about their lifestyle and treatment options, to maintain compliance with medical regimens, to communicate effectively with each other and healthcare professionals, and to listen to their own inner voice as they make decisions about the future. His website is JustGotDiagnosed.com.

FAMILY MATTERS

For the treatment of bleeding episodes in people* with hemophilia A or B with inhibitors

I’M READY TO MOVE ON Get rapid, predictable, and reliable † bleed control with SEVENFACT 225 Rapid effect: 3 hour At 3 hours, 84% of mild/moderate bleeding episodes were controlled with a single dose

Predictable response: 84% ‡

At 9 hours, 84% of mild/moderate bleeding episodes treated achieved bleed control after a single dose

Reliable control: 99.5% At 24 hours, 99.5% of mild/moderate bleeding episodes were resolved

Convenient home use: 98% 98% of bleeding episodes were treated at home † ‡

225 mcg/kg initial dosing regimen in the clinical trial. As seen in the clinical trial.

Summary of Selected Safety Information What is the most important information I should know about SEVENFACT? The most serious possible side effect of SEVENFACT is abnormal clotting involving blockage of blood vessels, which include stroke, blockage of the main blood vessel to the lung, and deep vein blood clots. You should know the signs of abnormal clotting and seek medical help immediately if they occur. Signs of clotting in places other than your site of bleeding can include new onset of swelling and pain in limbs, new onset of chest pain, shortness of breath, loss of sensation or motor power, or altered consciousness or speech.

What is SEVENFACT?

SEVENFACT is an injectable medicine used for the treatment and control of bleeding episodes occurring in adults and adolescents 12 years of age and older with Hemophilia A or B with inhibitors. Injecting medicines requires special training; do not attempt to self-infuse unless you have been taught how by your healthcare provider.

Who should not use SEVENFACT (coagulation factor VIIa)? You should not use SEVENFACT if you are allergic to rabbits, or if you have known allergies to SEVENFACT or any of its components. Seek immediate medical help if you experience hives, itching, rash, difficulty breathing with cough or wheezing, swelling around the mouth and throat, tightness of the chest, dizziness or fainting, or low blood pressure after taking SEVENFACT. Tell your healthcare provider prior to using SEVENFACT if you have begun treatment of a bleeding episode with another bypassing agent.

What should I tell my healthcare provider before I use SEVENFACT? Tell your healthcare provider if you are pregnant, are nursing, or plan to become pregnant; if you have had prior blood clots, heart disease or heart failure, abnormal heart rhythms, prior pulmonary clots, or heart surgery; or if you have or have had any other medical conditions.

What are the possible side effects of SEVENFACT? The most common adverse reactions for SEVENFACT are headache, dizziness, infusion-site discomfort, infusion-site hematoma, and infusion-related reaction and fever. Seek immediate medical help if you have signs of a blood clot or an allergic reaction. To report SUSPECTED ADVERSE REACTIONS or product complaints, contact HEMA Biologics at 1-855-718-4362. You may also report SUSPECTED ADVERSE REACTIONS to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please see Patient Product Information on the next page.

NEW

Coagulation Factor VIIa (Recombinant)-jncw

Make the move

Musculoskeletal

Ultrasound

Testing Comes to

n July 2019 at the National LadyBugs Women’s Summit in Santa Fe, New Mexico, the Miami Hemophilia Treatment Center team of Drs. Kelli Fraga DPT, Rachel Leeman MD, Fernando Corrales Medina and Leandro Pisani provided Musculoskeletal Ultrasound (MSKUS) on Women with Bleeding Disorders to assess joint health. CHES has a long-term commitment of providing research opportunities

at their programs for members of the bleeding disorder community. Plans are underway to continue this study in 2021 at a (hopefully) live LadyBugs Women’s Summit October 1-3, 2021. This poster abstract was presented at the Thrombosis and Hemostasis Summit of North America (THSNA) in October 2021.

int-of-Care M , Lawrence P. Cahalin DPT, Maria Bastos MD t Health Using Po man MD MD ga DPT, Rachel Lee F Corrales-Medina

Assessment of Join

nando Kelli A. Fra nna A Davis MD, Fer Treatment Center Leandro Pisani Joa Miami Hemophilia University of

sion

cus Conclusions and Dis

und oskeletal Ultraso Point-of-Care Muscul l knees, showing Images of bilatera l cartilage. thickness of femora

Results

HEAD US

BMI

29.4

Measurements:

2 ht/weight (kg/m ) Mass Index: Heig

LIFELINES for HEALTH

HJHS

HEAD US vs BMI

References

9 8

HEAD US Score

7 6

r=.680; p=0.011

30 20

r=.610; p=0.027

4 3 2 1 0

10 Pictured above: 1. Goniometric measurements for HJHS score 2. Atrophy of right gastrocnemius muscle, clinically significant of chronic ankle pathology

BMI

HEAD US vs HJHS

BMI

with Ultrasound opathy Detection are ophilia Early Arthr ankles. The joints HEAD-US: Hem elbows, knees and ces (0-4) ination of bilateral to articular surfa ge dama Ultrasound exam se 0-48 with activity (0-2), disea s can range from score scored on disease -US (0-2). Total HEAD and bone changes arthropathy ating more severe higher scores indic ing Score lia Joint Health includes the follow ophi Hem : HJHS s, and ankles that es nt of elbows, knee gth and gait. Scor Clinical assessme ROM, pain, stren irment atrophy, crepitus, ating greater impa aspects: swelling, higher scores indic with 48 to 0 range from among body test was calculated a : Pearson correlation two variables with Statistical Analyses -US, comparing ), HJHS, and HEAD p<0.05. mass index (BMI ficance was set at signi of level two-tailed test. The

nship t showing the relatio Figure 1: Scatterplo very HJHS. A significant, between BMI and lation was identified. strong positive corre

42.1

37.5

10 5

24.7

36.2

r=.917; p=0.000

25.6

9 10

27.9

54.5

33.7

l joint changes. onstrates subclinica ing disorders dem treatment of women with bleed early detection and on of MSKUS testing of lish protocols for rse the progressi be used to estab to prevent or reve ders These findings could disor ing women with bleed joint changes in with bleeding en treatment to wom nsive hy. rehe opat comp arthr of time. ort the expansion joint changes over We propose to supp itor joint health and de MSKUS to mon g disorders to inclu . Additional testin le size of this study and further to increase the samp lts ed resu of plann is ce on fican Further investigati and joint fully increase signi ders hope to disor ing year next with bleed will be done in the care for women of obesity in for comprehensive higher incidence support the need rmine if there is a es needed to dete ral population. health. Further studi ared to the gene ing disorders comp women with bleed

BMI vs HJHS

35.4

Clinical Relevance

dislocation, ria such as a fracture, Exclusion Crite to the knee or ankle ent during the past History of an injury ring medical treatm ent damage requi cartilage or ligam cement. repla joint of ry year or any histo BMI: Body

cts

collected of 13 subje

HJHS

ages 18 to

Mild Hemophilia 57%

Type 1 VWD 14%

Subject #

Methods

DIAGNOSIS

Factor VII Deficiency 22% Type 3 VWD 7%

Table 1: Raw data

HEAD US Score

nship t showing the relatio icant, Figure 2: Scatterplo signif Score and BMI. A between HEAD US lation was identified. strong positive corre

Spring/Summer 2021

Disorders

ing disorders was women with bleed weight/obesity in lation between BMI prevalence of over e is strong corre ges in joint In this sample, the ral population. Ther to evaluate chan identified in the gene g S is a valuable tool HJH . higher than that risk for developin D-US at HEA also as BMI and this population is use beca and HJHS as well ders with bleeding disor health in women se. disea joint joint nic chro ss weight and ns between exce lished associatio ence of chronic borate the estab an increased incid Our findings corro cipants could have s in joints, therefore weight study parti compressive force stress. The over include small ht creates more study weig this r to s highe a l bleeds. Limitation arthropathy since the risk of subclinica der diagnoses. potentially increasing ent coagulation disor the inclusion of differ sample size and

Introduction

t ght to primarily affec tionally been thou health. ophilia, have tradi ing disorders' joint , particularly hem women with bleed Bleeding disorders at a higher risk of literature regarding are in ts, gap a effec is males, so there omic and hormonal ophilia A and B ral, by virtue of anat are men. Female carriers of Hem changes which Women, in gene , manifesting joint joint problems than ses and omy and hormones developing chronic of acute hemartho ional impact of anat to the development er gend experience this addit of n of the contributio men and raise the question oses occur in both hy. arthr opat hem l arthr nts linica nic patie subc chro 23% of nce that clinical and demonstrated that joint There is now evide as well. A study The presence of ted joint bleeds. r bleeding disorder ture. (VWD) self-repor women with othe ribed in the litera Willebrand Disease rarely been desc suffering from von ing disorders has bleed rare with disease in people with bleeding health in women S. Objective: acteristics of joint protocol and HJH prevalence and char (MSKUS) score To determine the eletal Ultrasound validated Musculosk disorders using a

patients Inclusion Criteria includes female ing disorders group Women with bleed a bleeding disorder. rmed diagnosis of 50 years with confi

en with Bleeding

asound in Wom usculoskeletal Ultr ,

HJHS

nship t showing the relatio Figure 3: Scatterplo .A Score and HJHS fied. between HEAD US correlation was identi significant positive

method for dure and scoring ified scanning proce . 109(6): p. b Haemost, 2013 definition of a simpl Development and (HEAD-US). Throm Martinoli, C., et al., tion with Ultrasound i P, Arthropathy Detec o-Johnson M, Petrin Haemophilia Early Manc M, ont CS, McLim 1170-9. trom BM, Bradley . Haemophilia. 2006 Zourikian N, Bergs score reliability study Hilliard P, Funk S, . philia joint health Feldman BM. Hemo 516.2006.01312.x. PMID: 16919083 vs dual van den Berg M, BMI and skinfolds 365-2 by 11/j.1 ents urem 10.11 Obes., . doi: of body fatness meas risk factors in adolescents. Int. J. Sep;12(5):518-25 al., 2005. Comparison vascular Steinberger, J. et relation to cardio ptiometry and their energy X-ray absor 352. 29(11), pp.1346–1 their annual g on subjects at us to conduct testin dation for allowing Lady Bugs Foun Thank you to the bleeding disorders. with en Wom summit for

Acknowledgement

BLOODLINES

Introduction Introduction Introduction

Bleeding disorders, particularly hemophilia, have traditionally been thought to primarily affect males, so there is a gap in literature regarding women with bleeding disorders' joint health. Bleeding disorders, particularly hemophilia, have traditionally been thought to primarily affect Women, general, by virtue of anatomic and hormonal effects, are thought at a higher risk of affect Bleedingindisorders, particularly hemophilia, have traditionally been to primarily males, so there is a gap in literature regarding women with bleeding disorders' joint health. developing chronic than are men.women Femalewith carriers of Hemophilia A and B males, so there is ajoint gapproblems in literature regarding bleeding disorders' joint health. Women, in this general, by virtue of anatomic andand hormonal effects, are at a joint higher risk of which experience additional impact of anatomy hormones, manifesting changes Women, in general, by virtue of anatomic and hormonal effects, are at a higher risk of developing chronic joint problems than are men. Female carriers of Hemophilia A and B raise the question the contribution of gender to Female the development acute hemarthoses developing chronicofjoint problems than are men. carriers ofofHemophilia A and B and experience this additional impact of anatomy and hormones, manifesting joint changes which chronic arthropathy. experience this additional impact of anatomy and hormones, manifesting joint changes which raise the question of the contribution of gender to the development of acute hemarthoses and There is now evidence that clinical andofsubclinical occur in both men and and raise the question of the contribution gender to hemarthroses the development of acute hemarthoses chronic arthropathy. women other bleeding disorder as well. A study demonstrated that 23% of patients chronicwith arthropathy. There is now evidence that clinical and subclinical hemarthroses occur in both men and suffering von Willebrand Disease self-reported joint bleeds. The presence of joint There is from now evidence that clinical and(VWD) subclinical hemarthroses occur in both men and women in with otherwith bleeding disorder disorders as well. Ahas study demonstrated that 23% ofliterature. patients disease people rare bleeding rarely been described in the women with other bleeding disorder as well. A study demonstrated that 23% of patients suffering from von Willebrand Disease (VWD) self-reported joint bleeds. The presence of joint Objective: suffering from von Willebrand Disease (VWD) self-reported joint bleeds. The presence of joint disease in people with rare bleeding disorders has rarely been in described in the literature. To determine the prevalence and characteristics of joint women with bleeding disease in people with rare bleeding disorders has rarelyhealth been described in the literature. Objective: disorders using a validated Musculoskeletal Ultrasound (MSKUS) score protocol and HJHS. Objective: To determine the prevalence and characteristics of joint health in women with bleeding To determine the prevalence and characteristics of joint health in women with bleeding disorders using a validated Musculoskeletal Ultrasound (MSKUS) score protocol and HJHS. disorders using a validated Musculoskeletal Ultrasound (MSKUS) score protocol and HJHS. Table 1:

Subject1: # Table Table 1:

Subject # 1 Subject # 2 31 1 42 2 53 3 64 4 75 5 86 6 97 7 108 8 119 9 10 12 10 11 13 11 12 12 13 13

Methods Inclusion Criteria Methods Women with bleeding disorders group includes female patients ages 18 to Methods

Inclusion Criteria 50 years with confirmed diagnosis of a bleeding disorder. Inclusion Criteria Women with bleeding disorders group includes female patients ages 18 to Women bleeding disorders group patients ages 18 to 50 yearswith with confirmed diagnosis of a includes bleedingfemale disorder. Exclusion Criteria 50 years with confirmed diagnosis of a bleeding disorder. History of an injury to the knee or ankle such as a fracture, dislocation, Exclusion Criteria damage requiring medical treatment during the past cartilage or ligament Exclusion Criteria History of an injuryoftojoint the knee or ankle such as a fracture, dislocation, year or any history replacement. History injury todamage the kneerequiring or anklemedical such as treatment a fracture,during dislocation, cartilageoforanligament the past cartilage or ligament damage requiring medical treatment during the past year or any history of joint replacement. Measurements: year or any history of joint replacement. BMI: Body Mass Index: Height/weight (kg/m2)

Measurements: Measurements:

60 50

BMI

60 40 60 50 30 50 40 20 40 30 10 30 20 0 20 10 0 10 0 0 0 Figure0 2: BMI BMI

2) BMI: BodyHemophilia Mass Index:Early Height/weight (kg/m HEAD-US: Arthropathy Detection with Ultrasound BMI: Body Mass Index: Height/weight (kg/m2) Ultrasound examination of bilateral elbows, knees and ankles. The joints are HEAD-US: Hemophilia Detection with Ultrasound scored on disease activityEarly (0-2),Arthropathy disease damage to articular surfaces (0-4) HEAD-US: Hemophilia of Early Arthropathy Detection with Ultrasound Ultrasound examination bilateral elbows, knees and ankles. joints and bone changes (0-2). Total HEAD-US scores can range fromThe 0-48 withare Ultrasound examination of (0-2), bilateral elbows, kneesto and ankles.surfaces The joints are scoredscores on disease activity disease damage articular (0-4) higher indicating more severe arthropathy scored on disease activity (0-2), disease damage to articular surfaces (0-4) and bone changes (0-2). Total HEAD-US scores can range from 0-48 with and bone changes (0-2).more Totalsevere HEAD-US scores can range from 0-48 with higher scores indicating arthropathy HJHS: Hemophilia Joint Health Score higher scores indicating more severe arthropathy Clinical assessment of elbows, knees, and ankles that includes the following HJHS: Hemophilia Joint Health Score aspects: swelling, atrophy, crepitus, ROM, pain, strength and gait. Scores HJHS: Hemophilia Joint Health Score Clinical assessment of higher elbows,scores knees,indicating and ankles that includes the following range from 0 to 48 with greater impairment Clinical of elbows, knees, and pain, ankles that includes theScores following aspects:assessment swelling, atrophy, crepitus, ROM, strength and gait. aspects: swelling, atrophy, crepitus, ROM, pain, strength and gait. Scores range fromAnalyses: 0 to 48 with higher scores indicating greater impairment Statistical Pearson correlation test was calculated among body range from 0 to 48 with higher scores indicating greater impairment mass index (BMI), HJHS, and HEAD-US, comparing two variables with a Statistical Analyses: correlation calculated among body two-tailed test. The levelPearson of significance wastest set was at p<0.05. Statistical Pearson correlationcomparing test was calculated among mass indexAnalyses: (BMI), HJHS, and HEAD-US, two variables withbody a mass index (BMI), HJHS, and HEAD-US, comparing two variables with a two-tailed test. The level of significance was set at p<0.05. two-tailed test. The level of significance was set at p<0.05.

Pictured above: 1. Goniometric measurements for HJHSabove: score Pictured 2.Pictured of right 1. Atrophy Goniometric above: measurements for 1. gastrocnemius Goniometric muscle, clinicallyfor HJHS score measurements chronic 2. significant Atrophy ofofright HJHS score pathology gastrocnemius 2. ankle Atrophy of right

muscle, clinically gastrocnemius significant of chronic muscle, clinically ankle pathology significant of chronic ankle pathology

between H strong Figurepos 2: Figure between2:H between strong poH strong po

eandro Pisani Joanna A Davis MD, Fernando F Corrales-Medina MD University of Miami Hemophilia Treatment Center

rily affect health. ofaffect yaffect nd alth.B ealth. ges which hoses and B B ect s.which which and es sesand and ients nce d of joint nd hich ature. s nts and eofofjoint joint ding re. ure. d HJHS.

Point-of-Care Musculoskeletal Ultrasound Images of bilateral knees, showing thickness of femoral cartilage.

Results Results Results Results

y onic

Subject #

HJHS

HEAD US

HJHS 17 HJHS 37

HEAD US0 HEAD US 2

BMI

BMI 29.4 BMI 40

Table 1:1 Raw of 130 subjects 3 data collected 1 17 23 29.4 35.4

HEAD US vs BMI HEAD US vs BMI

40 BMI

5060 30

BMI

3040 10 2030

1020

010

42.1

r=.680; p=0.011 HEAD US vs BMI

4050 20

r=.680; p=0.011 0

4 6 8 r=.680; p=0.011 HEAD US Score

BMI vs HJHS BMI vs HJHS r=.917; p=0.000

40 50

HJHS

35 45 5030 40 4525

50 45 40

25 3010 20 25 5

BMIp=0.000 vs HJHS r=.917; r=.917; p=0.000

15 20 0 10 15 0

HJHS

35 4020 30 3515

p=0.000 BMI 5 r=.917; 10 0 5 0 20 30 40 the relationship 50 60 Figure 1:10Scatterplot showing 0 BMI 30 0 10 20 40 50 between BMI and HJHS. A significant, very 60

30 25 20 15 10

strong positive correlationBMI was identified. 5 Figure 1: Scatterplot showing the relationship 0 between BMI and HJHS. A significant, very60 Figure the 0 101: Scatterplot 20 30 showing 40 50 relationship HEAD US vs HJHS strong positive was identified. between BMIcorrelation and HJHS. A significant, very BMI 9 strong positive correlation was identified. 8 Figure 1: Scatterplot showing relationship HEAD US vsthe HJHS 7 between and HJHS. A significant, very 9 BMI 6 HEAD US vs HJHS strong 8positive correlation was identified. 5 9 7 4 r=.610; p=0.027 8 6 3 7 HEAD US vs HJHS 5 9

8 7 6 5

HEAD US Score HEAD US Score

HEAD US Score

29.4 40 33.7 BMI 40 35.4 33 35.4 33.7 54.5 29.4 33.7 33 20 40 33 54.5 27.9 35.4 54.5 20 25.6 33.7 36.2 27.920 33 27.9 24.7 25.6 54.5 25.6 37.5 36.2 20 36.2 24.7 42.1 27.9 24.7 37.5 25.6 37.5 42.1 36.2 42.1 24.7

HEAD US 0 vs BMI 37.5

17 00 37 28 2 3720 HEAD US 2 0 23 1 23 18 28 42 0 17 0 2813 00 20 0 37 2 20 00 42 11 8 23 1 42 13 16 0 82 28 0 111324 0 00 20 0 11 16 7 2 00 42 8 241625 0 20 13 0 24 7 33 0 00 11 0 25 7 0 0 16 2 25 33 0 0 24 0 33 0 7 0

HJHS

HEAD US Score

1 4 2 Subject # 2 5 3 3 6 4 1 4 7 5 2 5 8 6 3 76 9 4 8 7 10 5 9 8 11 6 10 9 12 7 1110 13 8 1211 9 1312 10 13 11

DIAGNOSIS DIAGNOSIS

DIAGNOSIS

Table 1: Raw data collected of 13 subjects Table 1: Raw data collected of 13 subjects Subject #1 Subject # 2

DIAGNOSIS

Factor VII Ultrasound Point-of-Care Musculoskeletal Deficiency Images of bilateral knees, showing 22% cartilage. thickness of femoral Factor VII Type 3 VWD Factor VII Deficiency Mild 7%Deficiency 22% Hemophilia 22% 57% Type 3 Type VWD1 VWD Mild Type 3 VWD 14% 7% Mild Hemophilia 7%VII Factor Hemophilia 57% Deficiency 57% Type 22% 1 VWD Type 14% 1 VWD Type 3 VWD 14% Mild 7% Hemophilia 57% Type 1 VWD BMI vs HJHS 14%

Table 1: Raw data collected of 13 subjects

Point-of-Care Musculoskeletal Ultrasound Point-of-Care Musculoskeletal Ultrasound Images of bilateral knees, showing Images of bilateral knees, showing thickness of femoral cartilage. thickness of femoral cartilage.

HJHS

goint JHS. HJHS.

above: ometric surements for S score hy of right cocnemius ents for e: le, clinically eicant ric of chronic right ments for pathology mius ore nically f right of chronic emius ology or linically t of chronic hology

In this sa higher th and HJH In this samp In this sa health higher thanin higher th andchronic HJHS aj and HJH health in wo health in In this Our sample, findi chronic joint chronic higher stress. than tha T and HJHS as w Ourarthropa findings Our find health potential in wome stress. The stress. T chronicsample joint dis s arthropathy arthropa potentially in potentia Our findings co sample size stress.sample The ove arthropathy sin potentially incre sample size an

Point-of-Care Musculoskeletal Ultrasound Images of Bilateral knees, showing thickness of femoral cartilage.

4 3 2 1 0

6 5 4 3 2

r=.610; p=0.027

1 0

r=.610; p=0.027 10 20

HJHS

0 4 6 10 0 1 r=.610; 20 showing 30 40 50 Figure 2: 2Scatterplot showing the 8relationship 4 p=0.027 Figure 3: 10 Scatterplot the relationship r=.680; p=0.011 0 HEAD US Score 0 20 HJHS 3 between HEAD US Score and BMI. A significant, between HEAD US Score and HJHS. A 0 2 4 6 8 10 0 10 20 30 40 2 10 strong positive correlation was identified. HEAD US Score significant positive correlation HJHS was identified. Figure 2: Scatterplot showing the relationship 1 Figure 3: Scatterplot showing the relationship 0 0 between HEAD US Score and BMI. A significant, between HEAD US Scoreshowing and HJHS. A 0 4 6 8 relationship 10 Figure 2:2 Scatterplot showing the 3: Scatterplot the 0Figure 10 20 30 40 relationship 50 strong positive correlation was identified. significant positive correlation was identified. HEAD US Score HJHS between HEAD US Score and BMI. A significant, between HEAD US Score and HJHS. A n n 40 LIFELINES for HEALTH Spring/Summer 2021 strong positive correlation was identified. significant positive correlation was identified. Figure 2: Scatterplot showing the relationship Figure 3: Scatterplot showing the relationship between HEAD US Score and BMI. A significant, between HEAD US Score and HJHS. A strong positive correlation was identified. significant positive correlation was identified.

MSKUS These f joint cha MSKUS tes MSKUS arthropa These findi These f prop jointWe chang joint ch disorde arthropathy MSKUS testin We arthrop propos These Further findings We pro disorders to joint changes disorde will be d arthropathy. support Further inv We propose to Further health. will be done disorders to in will be women support thed support health. Fur Further invest health. women with will be done in women support the ne Martinoli, health. Furthe Haemoph women with b 1170-9.

Martinoli, C., Hilliard P, Haemophilia E Martinoli, van den B 1170-9. Haemoph Sep;12(5) Hilliard P, Fun 1170-9. Steinberg Martinoli, C.,Berg et Pa van Hilliard den energy XHaemophilia EarB Sep;12(5):518 van den 29(11), pp 1170-9. Steinberger, Sep;12(5J Hilliard P, Funk energy X-rayS Steinberg van29(11), denenergy Berg M, pp.13 X Thank yo Sep;12(5):518-25 29(11), p summit fo Steinberger, J. e Thank youabs to energy X-ray summit for W 29(11), pp.1346– Thank yo summit fo

Thank you to the summit for Wom

ter enter Conclusions Conclusions andand Discussion Discussion In this In sample, this sample, the prevalence the prevalence of overweight/obesity of overweight/obesity in women in women with with bleeding bleeding disorders disorders was was higher identified ingeneral the general population. There is strong correlation between higher thanthan that that identified in the population. There is strong correlation between BMI BMI HJHS as well as BMI HEAD-US. and and HJHS as well as BMI and and HEAD-US. HJHS HJHS is a valuable is a valuable tool to tool evaluate to evaluate changes changes in joint in joint health health in women in women with with bleeding bleeding disorders disorders because because this population this population is also is also at risk at for riskdeveloping for developing chronic disease. chronic joint joint disease. findings corroborate the established associations between excess weight Our Our findings corroborate the established associations between excess weight and and joint joint stress. overweight participants an increased incidence of chronic stress. The The overweight studystudy participants couldcould havehave an increased incidence of chronic arthropathy a higher weight creates compressive forces in joints, therefore arthropathy sincesince a higher weight creates moremore compressive forces in joints, therefore potentially increasing the of risk of subclinical bleeds. Limitations to study this study include potentially increasing the risk subclinical bleeds. Limitations to this include smallsmall sample the inclusion of different coagulation disorder diagnoses. sample size size and and the inclusion of different coagulation disorder diagnoses.

und und

SIS NOSIS

Mild Mild emophilia mophilia a 57% 57%

Clinical Clinical Relevance Relevance MSKUS MSKUS testing testing of women of women with with bleeding bleeding disorders disorders demonstrates demonstrates subclinical subclinical joint joint changes. changes. These findings be used to establish protocols for early detection treatment These findings couldcould be used to establish protocols for early detection and and treatment of of joint joint changes in women with with bleeding disorders to prevent or reverse the progression of of changes in women bleeding disorders to prevent or reverse the progression arthropathy. arthropathy. We propose to support the expansion of comprehensive treatment to women with with bleeding We propose to support the expansion of comprehensive treatment to women bleeding disorders to include MSKUS to monitor health and joint changes overtime. disorders to include MSKUS to monitor joint joint health and joint changes overtime.

50 5060

60 60

elationship elationship nship ant, ant, ery very very ntified. .tified.

Further investigation is planned to increase the sample of study. this study. Additional testing Further investigation is planned to increase the sample size size of this Additional testing willdone be done the next to hopefully increase significance of results further will be in theinnext yearyear to hopefully increase significance of results and and further support the need for comprehensive for women bleeding disorders support the need for comprehensive carecare for women with with bleeding disorders and and joint joint health. Further studies needed to determine if there is a higher incidence of obesity health. Further studies needed to determine if there is a higher incidence of obesity in in women bleeding disorders compared togeneral the general population. women with with bleeding disorders compared to the population.

References References

40 40 50

elationship nship lationship S. S. A A dentified. dentified. ed.

50 50

Martinoli, Martinoli, Martinoli, C., etC., C., al.,et etDevelopment al., al., Development Development and definition and and definition definition of a simplified of of aa simplified simplified scanning scanning scanning procedure procedure procedure and scoring and and scoring scoring method method method for for for Haemophilia Haemophilia EarlyEarly Arthropathy Arthropathy Detection Detection with Ultrasound with (HEAD-US). (HEAD-US). Thromb Thromb Haemost, Haemost, 2013.2013. 109(6): 109(6): p. p. Haemophilia Early Arthropathy Detection with Ultrasound Ultrasound (HEAD-US). Thromb Haemost, 2013. 109(6): p. 1170-9. 1170-9. 1170-9. Hilliard Hilliard P, Funk P, S, Zourikian S, N, Bergstrom N, BM, Bradley BM, CS, McLimont CS, M, Manco-Johnson M, M, Petrini M, P, P, Hilliard P, Funk Funk S, Zourikian Zourikian N, Bergstrom Bergstrom BM, Bradley Bradley CS, McLimont McLimont M, Manco-Johnson Manco-Johnson M, Petrini Petrini P, van den van den M, Feldman M, BM. Hemophilia BM. joint health joint scorescore reliability reliability study.study. Haemophilia. Haemophilia. 20062006 vanBerg den Berg Berg M, Feldman Feldman BM. Hemophilia Hemophilia joint health health score reliability study. Haemophilia. 2006 Sep;12(5):518-25. Sep;12(5):518-25. doi: 10.1111/j.1365-2516.2006.01312.x. doi: PMID: PMID: 16919083. 16919083. Sep;12(5):518-25. doi: 10.1111/j.1365-2516.2006.01312.x. 10.1111/j.1365-2516.2006.01312.x. PMID: 16919083. Steinberger, Steinberger, J. et al., J. al., Comparison Comparison of body of fatness fatness measurements measurements by BMI by BMI and vs dual vs Steinberger, J. et et2005. al., 2005. 2005. Comparison of body body fatness measurements byand BMIskinfolds and skinfolds skinfolds vs dual dual energy energy X-rayX-ray absorptiometry absorptiometry and their and their to cardiovascular to risk factors risk in adolescents. in Int. J.Int. Obes., J. energy X-ray absorptiometry and relation their relation relation to cardiovascular cardiovascular risk factors factors in adolescents. adolescents. Int. J. Obes., Obes., 29(11), 29(11), pp.1346–1352. pp.1346–1352. 29(11), pp.1346–1352.

Acknowledgements Acknowledgements

Thank Thank Thank you to you you theto toLady the the Lady Lady BugsBugs Bugs Foundation Foundation Foundation for allowing for for allowing allowing us to us us conduct to to conduct conduct testing testing testing on subjects on on subjects subjects at their at at annual their their annual annual summit summit for Women for with bleeding with disorders. disorders. summit for Women Women with bleeding bleeding disorders.

BLOODLINES

by Joanna Davis, MD

LIFELINES for HEALTH

Spring/Summer 2021

oming off a year of fear and uncertainty, isolation and separation, it is easy to understand that the world has changed. But amidst all the negatives, for families living with the challenges of Hemophilia A and Hemophilia B, there have been overwhelmingly positive steps as well. We are all familiar with Hemophilia A/B: inherited underproduction or lack of production of clotting factor 8/9 respectively, which predisposes affected persons to life- (and/or) limb-threatening bleeding with little or no trauma for those considered “severe” (basically not able to produce any factor 8/9). Thirty-five years ago, when the University of Miami Pediatric Hemophilia Treatment Center was established, it was an accepted fact: people with severe hemophilia will experience spontaneous joint bleeds. Fortunately, by that time, the infusion of factor concentrate was available to stop the bleeding episode and allow restoration of joint function. This “episodic” or “on-demand” infusion approach put the patient in a cycle of playing catch-up.

We now know that once there is any blood in a joint, the chemical and physiological responses start that joint on a path to possible arthropathy and destruction. The prescribed factor dosing, in units/kilogram of body weight, was pretty much a formula: If this type of bleed, for someone weighing X, give X times y units. Pretty simple, but, as we learned, not the best way to provide care. But, as per the World Federation of Hemophilia, the infusion of factor concentrate remains the gold standard for hemophilia management. Jump ahead to 2007 and Marilyn Manco-Johnson’s Joint Outcome Study. Building on study results from European nations, this proved in the US, that...

...using factor infusions to PREVENT joint bleeds (prophylaxis) was better for patients, allowing them to maintain joint health and therefore normalize their work/school/home lives.

BLOODLINES

Still pretty formulaic - this dose used this often, etc., etc. However, the concept of trough levels became part of the vocabulary used between patient and HTC team. The thinking was that, since severe hemophiliacs are subject to spontaneous joint bleeds, and moderate hemophiliacs (1 -5 % activity) are generally not so susceptible, wouldn’t it make sense to make sure that the person NEVER had less than 1 % factor on board - that is, the trough or lowest level right before the next infusion was at least 1%. BUT…. everyone is different. How do we know what factor dose, given how often, will allow an individual to achieve this protective trough? And…. factor replacement product options were exploding. Over the next decade, “extended half-life” concentrates hit the market, offering the potential of having an infusion last longer in the bloodstream, opening the door to fewer infusions per week while maintaining that “safe” trough level. Along the way, both patients and treaters enjoyed the realization that prophylaxis opened the door to participation in sports, and other activities. Treaters realized that, for some, the 1% trough was not high enough to be protective between one infusion and the next. And some patients seemed to “use up” the factor more quickly than others. We (parents/families and HTC team members) have known that our patients of all ages are individuals when it comes to interests and talents, but now we recognized the need to identify each patient’s unique metabolism of factor concentrates and learn how to adjust their prophylactic schedule in a way to keep them safe and fully engaged. But HOW??

LIFELINES for HEALTH

Spring/Summer 2021

Pharmacokinetics is the movement of a drug/medication through the body, from the moment it is taken in, to the moment it passes out. Following an infusion, factor level increases (the peak level) which depends on the dose infused and the individual’s response. Over time, the level falls as the factor is being used. About 12 hours after a standard factor 8 infusion, and 24 hours after an infusion of factor 9, the level of factor left is about 50% of the peak level. The number of hours it takes to reach that 50% level is called the Half-life for the individual. Following the levels over several days, until the patient’s baseline level is reached, creates a “pharmacokinetic” or PK graph. This information allows us to recommend not only the starting dose, but the interval between infusions which will maintain that lowest point of 1%. Very individualized – but each time a patient switches factor product, it needs to be repeated and there are several “time points” when the factor level is checked. This translates into several scheduled lab visits over days – weeks, to establish that curve. Isn’t there a better way?

Enter myWAPPS, an online app which relies on Population Pharmcokinetic data (PopPK), and allows any patient, on prophylaxis with any particular factor product, to learn his/her PK profile with only a few post-infusion blood draws.

To register on myWAPPS, you must have a PK report completed on www. wapps-hemo.org by your treating physician.

Utilizing a tool called Bayesian statistics, the program has a database of thousands of infusion data for Hemophilia A or B patients around the world, using a variety of different factor concentrates. This serves as the “population” under study. With this database, an individual patient, already on a prophylactic regimen, or switching product, has a peak level drawn. Fewer post-infusion levels are necessary - including the potential for only 1 post-infusion draw to feed into the database, and have the program generate that patient’s PK response to that infusion. The curve can be adjusted based on what you/your treater want to know, including the dose/interval which would allow a higher trough level and, therefore, greater protection at the lowest point to cover activities. Takeda/Shire has a similar program called My PK Fit. These are available to patients, so that they can reference their curve and figure out where their level is likely to be at a particular time. Going to play soccer? “ Hmmmm… I get pretty banged up, and it looks as if my level would only be about 2% this afternoon. Guess I should infuse a day early just to avoid a problem.” Of course, nothing is exact, and nothing is perfect. (None of my patients get the green light for American football, lacrosse, and wrestling, regardless!) But these tools and the recognition of the need for individualized prophylaxis will continue to allow our families to participate fully and safely where their interests and abilities lead. Talk to your HTC team to sign up to manage your unique lifestyle safely!

Dr. Joanna Davis Pediatric Hematologist Medical Director University of Miami, Miller School of Medicine Miami, FL

BLOODLINES

by Dr. Maureen Strafford

In our Volume 4 Winter 2014 edition of LifeLines for Health, we published this article on Mindfulness, as a method to managing pain and anxiety in the inhibitor community. Since then, mindfulness practice, and multiple apps abound to easily incorporate this routine into our daily lives. Fast forward to 2021, and we feel this article is more appropriate than ever. One full year into the COVID pandemic, and we are experiencing more anxiety, more mental health challenges than ever before. Gaining control over our swirling emotions is as easy as taking a breath. Give it a try!

Exploring the SCIENCE of

MINDFULNESS

indfulness is a word that we are hearing about quite a bit these days. In January 2014, Time Magazine had a cover story called “The Mindful Revolution” with the subtitle “Finding peace in a stressed out, digitally dependent culture may just be a matter of thinking differently.” Do a search on Amazon and over 9,893 books are found with the word “Mindfulness” in the title, including a book by U.S. Congressman Tim Ryan called “A Mindful Nation.” One might think that “Mindfulness” has just been discovered by our 21st century society. In fact, mindfulness and the use of mindfulness meditation techniques can be traced back to ancient meditative and contemplative practices and are seen in many, if not all, religious traditions. However, the practice of mindfulness techniques --- practiced in a non-religious, secular manner --- with the introduction of such techniques into health care settings, the classroom, the corporate world and even in the locker rooms of national athletic teams --- has increased dramatically over the last several decades. In 1979, Dr. Jon Kabat-Zinn introduced mindfulness meditation into mainstream medicine when the University of Massachusetts Stress Reduction Clinic was begun at the University of Massachusetts Medical Center in Worcester, MA. Patients with a variety of medical problems attended an 8-week, once a week meeting with a group of other patients and a leader. This course was called

LIFELINES for HEALTH

Spring/Summer 2021

Mindfulness-Based-Stress-Reduction (MBSR) and has now expanded to thousands of hospitals across the world where many thousands of patients have found improvement in symptoms including anxiety, pain, and depression from a wide array of diagnoses. But what do we mean when we say Mindfulness. The definition of Dr. Jon Kabat-Zinn has been widely quoted.

“Mindfulness means paying attention in a particular way; on purpose, in the present moment and non-judgmentally.” We have all experienced being “mindless.” We park our car in the morning and when we return at the end of the day, we have no memory where the car is. Where was our mind when we were parking our car? We were certainly “not paying attention on purpose.” We have also experienced how one thought can spiral into an entire narrative usually of doom and gloom or negative self-descriptions or we can create a fantasy pleasurable scene and miss the unfolding of the present moment. We may experience pain and fear and anxiety that leads to panic that leads to increased suffering. Mindfulness slows down the reactive, out of control thinking called rumination. Mindfulness can help us observe the moments when our pain is different, diminishes, even disappears. The word non-judgmental is so important.

When we stop labeling every experience as good or bad, we eliminate the reactivity that causes us additional suffering. The way we “practice” mindfulness starts with the formal practice of sitting meditation, or movement practices such as yoga, tai chi, or walking meditation. There is no “right” or “wrong” way to sit and meditate. The breath is a good anchor for our attention because it is always there and has a changing quality to it. We may attend to the breath and have the shopping list for dinner pop into our heads and pull our attention away. As a parent firmly but lovingly moves the wandering child away from the dangerous road, so too with attention to the breath, we bring our attention back to the breath without judgment – no statements that “I’m a lousy meditator” or “This isn’t working.” With this commitment to attention and awareness, we move away from reactivity and rumination and the tendency of the mind to create entire scenarios and screenplays that may be pleasant or unpleasant and move into the vibrant experience of the present. While MBSR courses were blossoming all over this country and internationally over the last several decades, research on MBSR was also exploding and describing the positive effects of this practice on both physical and mental health. Research — including a fascinating look at the brain with tools such as functional MRI (a scan of the brain where

areas that are stimulated “light” up on the scan) --- began to suggest that indeed the brain can change and areas where anxiety, anger, and fear “reside” in the brain have been shown to quiet down when a person meditates. Of great interest is that the practice of mindfulness may have long-lasting effects and that the “brain” does indeed change. The “ruts” created by years of rumination, anxiety, and worry begin to “smooth over” as practice time increases. Mindfulness meditation --- even after the basic 8 week MBSR course --- has demonstrated a strengthening of the immune system, significant amelioration of depression comparable to the use of anti-depressant medications and improvement in the symptoms of Attention Deficit Disorder

(ADD). The quality and quantity of excellent clinical research on the beneficial effects of mindfulness has exploded and drawn the attention of neuroscientists and other basics research scientists. Teachers, health care providers, veterans suffering from PTSD, prisoners, children and patients with a wide array of symptoms and challenges improve the symptoms of their diseases, diminish the risk of caretaker burnout, and uniformly report an improved quality of life, including improved relationships. So how does one learn “Mindfulness” and how does one implement the changes mindfulness can stimulate? We practice! The “formal” practice complements and strengthens the “informal” practice. The formal practice is the time we take to “practice” observing our experience in a different way. We can practice sitting and using the breath as our anchor. We can practice yoga and observe our movements in a mindful manner. We use the skills learned and practiced during formal sitting meditation to observe the simple activities of daily life with an energized and creative curiosity. This is the “informal practice” of mindfulness when we observe the sensation of the splash of water on our face, the feel of the weather on the skin, the taste of a small morsel of food and in this “informal” practice, we experience life in a more deeply felt manner with less reactivity and suffering. We also experience benefits in the informal practice of mindfulness when we have pain or anxiety. We may observe moments when our pain is intense and moves to areas of our body and even a moment when the pain disappears. We learn that we are not our thoughts and we can move away from the “over and over” rumination of our worried mind.

How does one train or learn more about mindfulness and how to include it as part of a health self-care regimen? There are now programs throughout the US, many based in hospitals that may be covered by health insurance. There are also therapists who have been trained in MBSR and offer traditional 8-week MBSR courses. A review of the UMass Center for Mindfulness website - https://www. umassmemorialhealthcare.org/ - is a wonderful place

MIND BODY CONNECTION

to start in understanding the training required for MBSR teaching. A web search for MBSR courses and teachers in your area will be a productive place to start and after reviewing the UMass site, you will have good questions to ask when looking for MBSR courses. While programs are more limited for children, local mindfulness teachers can guide one in finding well-qualified teachers for children. There are increasing resources in books and apps that will also be helpful and asking your child’s pediatrician and teachers can also be a helpful place to start. The 8-week MBSR course is very helpful if doing it on your own is more difficult, and the group format adds to the insights gained as one progresses through the course. For those who are interested in more individual work or want to investigate a bit more on your own before committing to an MBSR course, there are many books, online courses and apps to help you. We have a wealth of resources to learn about Mindfulness and the effect on health, well-being and relationships. But even before one Internet search or book is ordered, remember we always have our breath. Our anchor. Sitting here reading, take a moment to find your place in your seat.

Slowly bring attention to bringing your shoulders back, and moving your body into a more upright position, slowly close your eyes if that feels comfortable where you are and bring your attention to that part of your body where the breath is noted – the nostrils, the upper chest, the belly. Notice how the quality of the breath changes with breathing in and breathing out. Notice how thoughts, “I don’t have time right now.” “I think this is not going to work.” “I can’t forget to send the check.” pop into the mind like popcorn being cooked. And with the gentle firmness and kindness of the parent moving the child off the dangerous road, bring your attention back to the breath. Some days, you may find yourself pulling the wandering mind back after every breath. That’s practice …. not “bad” meditation because there is no “good” or “bad” meditation. A great start to understanding mindfulness is with you at all times --- your breath. As a parent, you might find it helpful to do some practice and observe the positive effects with yourself before introducing some of the practices to your child. The introduction of mindfulness into the classroom has found positive results. Better classroom management and calmer children result when mindfulness has been utilized and teachers feel less stress as well. Programs such as the Mind-Up Program https://mindup.org/ and Mindful Schools (www.mindfulschools.org) have established programs, free resources and videos. The following is an overview of books, programs and apps available that may be helpful as you seek out more information about mindfulness.

Dr. Maureen Strafford, was the Associate Professor of Anesthesia and Pediatrics, Tufts University School of Medicine. The study of the effects of pediatric pain and the positive effects of mindfulness has been a career long concentration. We sadly mourn her passing in September of 2019.

Suggested Mindfulness Resources This is a small list of what is available as you investigate mindfulness. You will be amazed at the wealth of information available by simply typing Mindfulness into a Google Search! YouTube and the App Store provide many other tools that you may find helpful.

Getting Started

Online Courses

Learn about Jon Kabat Zinn, founder of the world-renowned Mindfulness-Based Stress Reduction Clinic (in 1979), and the Center for Mindfulness in Medicine, Health Care, and Society (in 1995) at the University of Massachusetts Medical School in Worcester MA.

This is a great way to start if you cannot attend a live MBSR (Mindfulness-Based-Stress-Reduction) course. The online course is taught by one of the senior teachers at UMass. https://www.umassmemorialhealthcare.org/umassmemorial-center-mindfulness

https://www.mindfulnesscds.com/ Here you will find scientific articles, books, videos and resources that explain mindfulness and its benefits. YouTube https://www.youtube.com/results?search_query=jon+kabatzinn+guided+meditation

LIFELINES for HEALTH

Spring/Summer 2021

UCLA has an incredible center for Mindfulness and online courses are available here as well with excellent and experienced teachers https://www.uclahealth.org/marc/ default.cfm?id=1

FOR CHILDREN & TEENS

Dr. Amy Salzman is a pediatrician who has developed programs for children. She has wonderful tapes and a book on mindfulness for Great resource for information about mindfulness in the schools. children, especially young children. A very detailed curriculum that http://www.stillquietplace.com is in place in many schools to teach children about stress, Gina Biegel is a therapist who has developed and researched a program mindfulness and coping skills. on mindfulness for teens. At her website, you can access many of her http://www.mindfulschools.org tapes, her workbook for teens and a wonderful CD for “stressed teens.” A very detailed curriculum that is in place in many schools to teach children about stress, mindfulness and coping skills. https://mindup.org/about/

FOR PARENTS

http://www.stressedteens.com Susan Kaiser Greenland has published a book called The Mindful Child and it is written for parents and incorporates many helpful tools for teaching mindfulness to children. http://www.susankaisergreenland.com

PAIN Everyday Blessings: The Inner Work of Mindful Parenting

The following are helpful when one is interested in helping manage pain.

For all parents who find the most important job of parenting sometimes stressful, Jon and Myla Kabat-Zinn have published a wonderful book on the topic of Mindful Parenting that is a delight to read and a great resource. It is now in a second edition. http://www.amazon.com/EverydayBlessings-Inner-Mindful-Parenting/ dp/0786883146 Full Catastrophe Living (Revised Edition): Using the Wisdom of Your Body and Mind to Face Stress, Pain, and Illness Another book which is a guideline to the format of an 8-week MBSR course is also in a revised edition and written by Jon Kabat-Zinn. http://www.amazon.com/FullCatastrophe-Living-Revised-Illness/ dp/0345536932/ref=sr_1_1?s=books&ie =UTF8&qid=1418857428&sr=1-1

The Minfulness Solution to Pain Step-by-Step Techniques for Chronic Pain Management, by Jackie Gardner-Nix http://www.amazon.com/MindfulnessSolution-Pain-Step-Step/dp/1572245816 Mindfulness Meditation for Pain Relief Guided Practices for Reclaiming Your Body and Your Life, by Jon Kabat-Zinn https://www.amazon.com/MindfulnessMeditation-Pain-Relief-Reclaiming/dp/ B0035YCZNS Mindful.org A great website to start for Mindfulness and Pain Management. Below is a direct link to the pain management portion of the site. http://www.mindful.org/Health%20and%20Healing/mindfulnessand-pain

APPS

DEVICES TO TRY

Mindfulness apps for Android or IOS or are numerous and many are free. Some are tools for helping you in your practice — reminders, guided meditation recordings, suggestions for mindful breaks during a busy day. Here are several free apps to get you started.

Finally, if you are interested in a new tool that gives a “visual” about your mind quieting down, take a look at a new device called “Muse.”

www.headspace.com

www.calm.com

https://my.life

https://insighttimer.com

As described on their website, “Muse detects your brain signals during guided focused attention exercise. It provides valuable feedback that you use to train your brain today and over time.” For some, this interesting interaction between the visual of seeing on a screen how you are agitated or able to calm down is very helpful. http://www.choosemuse.com

MIND BODY CONNECTION

89 E. Washington Street Hanson, MA 02341-1125

CHES Mission To Inspire awareness and selfreliance for patients with chronic health conditions, their families, and their communities.

Editors in Chief Janet Brewer, M.Ed Eric Lowe

Editor Janet Brewer, M.Ed

Publication Designer Eric Lowe

Contributing Writers Janet Brewer, M.Ed Gwen Cooper Joanna Davis, MD Barb Forss Angela Lambing, MSN, ANP, GNP Eric Lowe Gary McClain, PhD Jonathan C. Roberts, MD James Romano Maureen Strafford, MD

Contributing Materials Miami Hemophilia Treatment Center Giving a contribution to support the newsletter:

Stay Connected

__________________________________________________

Subscribe for Free If you have received this newsletter from another individual, and you wish to receive your own personal copy, please contact us via any of the following methods. Email: info@ches.education Office: 781.878.8561 Online: https://ches.education/communications-profile-form __________________________________________________

Online Version View this publication online for access to helpful links, cited resources, and other great add-ons at: https://ches.education/newsletter/ __________________________________________________ DEAR HEALTH CARE PROVIDERS, PLEASE CIRCULATE TO PATIENTS.